Researchers Use Novel 3D Imaging To Track Alzheimer's

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Using an innovative three-dimensional imaging technique, a team of UCLA researchers have tracked how Alzheimer's disease spreads through the hippocampus - the area of the brain linked with memory - in a pattern consistent with the known trajectory of neurofibrilliary tangle dissemination, an accumulation of diseased proteins in the brain cells. They found that three areas within the hippocampus of Alzheimer's patients show more atrophy compared with those in patients having amnestic mild cognitive impairment (MCI), a recently defined condition characterized by memory decline but that leaves other daily living activities unimpaired, and which immediately precedes Alzheimer's.

IMPACT: The technique is significant because it makes it possible to track the progression of Alzheimer's disease in live patients. This will be crucial in evaluating the effectiveness of drugs that fight Alzheimer's when they become available for clinical trials.

AUTHORS: Liana G. Apostolova, Rebecca A. Dutton, Kiralee M. Hayashi, Arthur W. Toga, Jeffrey L. Cummings and Paul M. Thompson, all of the David Geffen School of Medicine at UCLA, and Ivo D. Dinov of the UCLA Department of Statistics.

FUNDERS: The National Institute of Aging, the American Federation for Aging Research, the National Institute for Biomedical Imaging and Bioengineering, the National Library of Medicine, the National Center for Research Resources, the National Institute for Mental Health, the National Institutes of Health, the National Science Foundation, the American Federation for Aging Research, the John A. Hartford Foundation, Atlantic Philanthropies, the Starr Foundation and an anonymous donor.

Alzheimer's jab trial resurrected

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Research into a vaccine for Alzheimer's disease, which was stopped early on safety grounds, is to be resurrected.
It was designed to reverse the disease's progression by clearing the beta amyloid protein that causes the disease.
But the trial was halted in 2002 when 6% of patients in the second phase of the study developed brain inflammation.
Southampton University researchers are to reassess 80 patients who took part in the initial phase of the study.
They will look at whether features of the disease such as memory loss have been halted or reversed.
The vaccine, known as AN-1792, contains a synthetic form of beta amyloid protein.
It acts by stimulating an immune response to the protein.
Preliminary results from the trial showed the vaccine did clear the amyloid protein from the brain.

Vaccine 'realistic prospect'
James Nicoll, professor of neuropathology at Southampton University Hospitals NHS Trust, who is leading the research, said: "This study offers us a unique insight into whether immunisation against Alzheimer's is an effective solution to this devastating disease.
"We know that vaccination can reverse the processes of Alzheimer's to some degree - our challenge is to understand these processes better and translate them into real benefits for patients."
Rebecca Wood, Chief Executive of the Alzheimer's Research Trust, said: "The prospect of a vaccine to protect against Alzheimer's is a realistic one because it is a disease, and not a normal part of ageing.
"Immunisation is an exciting area and we are delighted to be funding this groundbreaking study."
Clive Ballard, director of research at the Alzheimer's Society, said: "There are 25 million people worldwide with Alzheimer's disease and 100 000 people are diagnosed in the UK each year.
"This clearly highlights the urgent need to develop new ways of defeating dementia.
"The vaccine is one of the most exciting treatments for Alzheimer's and we are very please to see ongoing funding in the UK as part of a international effort to develop a vaccine for Alzheimer's disease."

CENTER OF GRAVITY - Alzheimer’s disease

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OF the afflictions of the aged, none is more devastating than Alzheimer’s disease. It destroys the brain. A lifetime of memories, a person’s most precious and unique possession, are lost.
The disease is named after Alois Alzheimer, a German physician, who first identified it about a hundred years ago.
There are two key features of the disease. Plaques and tangles of proteins are present in the cerebral cortex and the limbic system, the seat of the brain’s higher functions.
The question that exercised scientists all throughout the 20th century was: Are these plaques and tangles the cause of the degeneration of neurons in the brain?
Recent findings have partly answered the question. They are. The plaques are proteins called amyloid-beta, (A-beta for short) outside a neuron. The tangles are inside a neuron and its branches. They are a protein called tau.
A-beta is a short peptide of a larger protein, an amyloid-beta precursor (APP), that’s derived from the action of two enzymes, beta-secretase and gamma-secretase.

Most scientists now agree that the amyloid is the main cause of Alzheimer’s. The strongest evidence was the discovery of a rare genetic mutation that encodes the APP. This was discovered in 1991 by John A. Hardy and his associates at the US National Institute of Aging.
In 1995 Peter St. George-Hyslop and his colleagues at the University of Toronto in Canada discovered mutations in two related genes that were the cause of the early (before age 60) onset of Alzheimer’s.
Mutations in the tau gene have been identified but researchers are convinced that it is A-beta that’s the “specific initiator,” to use Michael Wolfe’s phrase in his article in the May 2006 issue of Scientific American.

Current research is focused on three procedures: inhibition, immunization and cell therapy.
To slow down cognitive decline some drugs that have been developed and approved for other diseases seem to have an inhibitory effect. A drug for the treatment of prostate cancer and a medicine for diabetes have halted, albeit temporarily, cognitive impairment.
Other compounds, including statins, normally for lowering cholesterol, are also showing promise.
Prescription drugs like Aricept, Exelon, Razadyne and Namenda have brought down cognitive deterioration to, at most, 18 months.
None of these medicines attack the underlying causes of Alzheimer’s. They, however, might eventually be helpful in arresting early signs of Alzheimer’s.
Since the A-beta is the main initiator, the proteases that produce this peptide are the object of investigation. In 1999, five research groups discovered independently of each other a protease that cuts off most of the APP outside the cellular membrane. The 3-dimensional model of beta-secretase is serving as a kind of guide or template to design an inhibitor.
But this is only the first step in the formation of A-beta. The second step is performed by the enzyme gamma-secretase. Bart de Strooper of the Catholic University of Louvain in Belgium found a way to delete the gene that’s essential to the functioning of the gamma-secretase enzyme.
If all this is successful it’s possible to find not just a treatment but maybe a cure for Alzheimer’s.
The other procedure is immunization. One approach is active immunization that involves using a patient’s own immune system to attack A-beta. Animal experiments have prevented the formation of plaques in the brain of young mice. Human trials were stopped in 2002 because some patients in a Phase II test developed an inflammation of the brain called encephalitis.
Safety concerns forced researchers to resort to passive immunization. The aim is to clear the A-beta by injecting antibodies into patients. This procedure is now in Phase II trials.
The third procedure is cell therapy. Mark Tuszynski pioneered it at the University of California in San Diego. In the cells of patients with mild Alzheimer’s, he inserted a gene that encodes for nerve growth factor (NGF). These genetically modified cells were implanted in the forebrain of a patient. The implanted cells produced NGF, preventing the loss of a neurotransmitter called acetylcholine, thus improving memory.
All throughout the 20th century, it was thought that Alzheimer’s disease could not be treated or cured. Hundreds of thousands of old people wasted away, becoming ciphers, even within the bosom of their own families.

But today there’s a glimmer of hope. If any or all these procedures prove safe and effective, our parents and grandparents who suffer from Alzheimer’s need not depart this world without recognizing or remembering their own children.
By Rony V. Diaz

Hope Remains For Alzheimer's Sufferers
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The National Institute of Clinical Excellence (NICE), who last week rejected appeals to allow patients with mild Alzheimer's to receive the life-changing medication donepezil (Aricept®), will hopefully re-appraise their decision in 3 years time, according to neurologist Professor Robert Kerwin in an article published in the November issue of the medical journal Future Neurology.

Kerwin evaluated recent research published in the Lancet that may not have been taken into account by the NICE committee. In this study, nursing home patients with severe Alzheimer's disease were administered with donepezil, or a placebo drug, and were observed for 6 months. Those patients receiving donepezil treatment showed significantly improved cognitive function, compared with those patients not receiving the drug, despite recommendations by NICE not to prescribe donepezil to this patient group. Kerwin also evaluates recent data suggesting that the drugs are effective in patients with milder forms of Alzheimer's disease.
The recent 2005 NICE revised guidelines for cholinesterase inhibitors, the class of drug that donepezil and other Alzheimer drugs rivastigmine (Exelon®/Prometax®) and galantamine (Reminyl®) belong to, state that these drugs can only be administered to patients with moderate Alzheimer's, for whom NICE believe the evidence is strongest. At the same time NICE withdrew its recommendations for the use of these drugs for patients with mild-to-moderate Alzheimer's. Memantime (Exiba®), belonging to another class of drugs, is not recommended to Alzheimer's sufferers, but is restricted to ongoing clinical trials and may be possible treatment in the future.
"NICE's decisions are based upon the economic health calculations that they do, which are balanced against clinical benefit. Even though the drugs do work in the long-term, patients do progress to requirements of alternative care that do not necessarily lead to savings within the NHS." Commented Kerwin, who is a Professor of Clinical Neuropharmacology at the Institute of Psychiatry, London.
750,000 people are estimated to suffer from Alzheimer's disease in the UK alone, with 78,000 of these receiving rivastigmine, galantamine and memantine; a further 2-thirds of sufferers take donepezil. Since NICE's original 2001 guidelines that this family of drugs should be made broadly available within the UK NHS for mild-to-moderate Alzheimer's disease, prescriptions have risen sharply and many sufferers have experienced a welcome relief from the debilitating symptoms of memory loss and cognitive decline.

Britain developing new treatments for Alzheimer's

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British scientists have created a new chemical compound that could be developed into a drug treatment for Alzheimer's disease.
UK researchers at the University of Liverpool have used a family of long chain sugars called Heparan Sulphates (HS), found on nearly every cell of the body, to produce a new compound that can prevent the formation of clumps of small proteins that form inthe brain, the science website Alpha Galileo reported on Thursday.
The clumps disrupting the normal function of cells leading to progressive memory loss which is characteristic of Alzheimer's disease, are formed from a small protein fragment called Amyloid-beta (A-beta) peptide released from its "parent" protein – amyloid precursor protein (APP), and the process requires the action of an enzyme called beta-secretase (BACE), critical in clipping up the APP to form the smaller A-beta fragments.
The researchers have discovered that the HS sugars may play a key role in limiting the development of Alzheimer's disease. The sugars stick to the BACE enzyme and reduce its ability to "clip" the A-beta peptide, thus controlling the amount of A-beta peptide available to form damaging clumps in brain tissue.
"We have developed a new class of compounds called 'engineered heparins' that could possibly be developed into drugs to stop A-beta peptides in the brain from forming and for the first time treat the underlying cause of Alzheimer's," leading researcher Professor Jerry Turnbull was quoted as saying.
The compound, based on the blood thinning drug, heparin, has modified chemical structures designed to optimize their desired activities and reduce potential side effects, and the compounds work by blocking the beta-secretase enzyme, responsible for snipping proteins into smaller fragments, he said, adding that despite its central importance to the disease, there are currently no drug treatments which target this enzyme because it has proved difficult to find inhibitors using traditional drug discovery approaches.
The new compounds, based on the body's natural substances, may provide a novel route to effective treatments for this debilitating disease -- Alzheimer's, the researchers said.
A spin-out company, IntelliHep Ltd, has been founded to explorethe commercial opportunities of developing engineering heparans asnew drugs against Alzheimer's and other important medical conditions, according to the report.

Alzheimer's alarm over anesthetics

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GIVING elderly patients certain general anaesthetics could increase their risk of developing Alzheimer's disease and other memory and attention problems.

The suggestion arises from recent test tube and animal experiments. They also indicate that anaesthetists need to log more carefully the combinations and doses of the anaesthetics they give to patients, to allow the risks to be properly assessed.
The link between surgery and cognitive problems was first noted during the 1950s, but it was never clear whether postoperative cognitive dysfunction (POCD) was the result of the surgery itself or the anaesthetics, says Pravat Mandal of the University of Pittsburgh Medical School in Pennsylvania. It has been suggested that heart bypass surgery in particular could make the protective blood-brain barrier leaky, allowing immune tissue or unwanted debris into the brain.
Now animals studies and test tube experiments are beginning to show that certain anaesthetics reduce the rate at which brain cells are born and develop, a factor that seems to be important to normal memory function. They may also directly affect the rate at which beta amyloid proteins bind together. This could be worrying, as the formation of clumps or "plaques" of these proteins is characteristic of Alzheimer's disease and may contribute to brain cell death.
Last week at the annual meeting of the Society for Neuroscience in Atlanta, Georgia, Mandal revealed that the inhaled anaesthetics halothane and isoflurane encourage clumping of beta amyloid protein, as does the commonly used intravenous anaesthetic propofol, at least at higher concentrations. The findings back up a previous study in which Mandal used NMR spectroscopy to show that halothane interacts directly with a pocket in the beta amyloid protein, changing its shape and encouraging neighbouring proteins to bind. Just 6 hours of exposure to halothane is sufficient to trigger protein clumping similar to that seen in people with Alzheimer's, he says.
Although halothane is rarely used in North America or Europe, it is commonly used in Asia and Africa because it is very cheap. "It is a seriously deadly combination when an older person receives halothane," says Mandal, because as we get older we all have more beta amyloid in our brains. The other anaesthetics studied are more widely used in the US and Europe, often in combination, though these seem to take longer to exert their potentially deadly effects. The good news is that the intravenous anaesthetic thiopental (known as thiopentone in the UK) appears to have no effect on the proteins.
Andy Jenkins of Emory University in Atlanta, Georgia, who studies the mechanisms of anaesthetic action, agrees that there are now plenty of anecdotal reports about elderly relatives never being quite the same after going in for surgery.
The problems seem to be most often associated with elderly patients undergoing long procedures such as heart bypass surgery or hip replacement. The new findings are important, he says, because doctors have not always carefully recorded which anaesthetics are used for each patient, nor are the follow-up methods for recording cognitive decline standardised.
At the same meeting, Jeffrey Sall from the University of California, San Francisco, showed that giving isoflurane to 7-day-old rat pups had effects on memory that lasted until adulthood. Fewer new brain cells developed in the memory regions of anaesthetised rats compared with control rats, suggesting that a decline in the rate of new cell birth – which seems vital for normal memory function – may persist long after receiving anaesthetics.
Now the warning has been sounded, Mandal hopes that the dangers and benefits of each anaesthetic will be urgently studied. "The main focus should now be using an anaesthetic that does not have any undesirable and deadly effects," he says.

Vegetables, Not Fruit, Help Fight Memory Problems In Old Age

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Eating vegetables, not fruit, helps slow down the rate of cognitive change in older adults, according to a study published in the October 24, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology.
In determining whether there was an association between vegetables, fruit and cognitive decline, researchers from Rush University Medical Center studied 3,718 residents in Chicago, Illinois, who were age 65 and older. Participants completed a food frequency questionnaire and received at least two cognitive tests over a six-year period.
“Compared to people who consumed less than one serving of vegetables a day, people who ate at least 2.8 servings of vegetables a day saw their rate of cognitive change slow by roughly 40 percent, said study author Martha Clare Morris, ScD, associate professor at Rush University Medical Center in Chicago, Illinois. “This decrease is equivalent to about 5 years of younger age.”
Of the different types of vegetables consumed by participants, green leafy vegetables had the strongest association to slowing the rate of cognitive decline. The study also found the older the person, the greater the slowdown in the rate of cognitive decline if that person consumed more than two servings of vegetables a day. Surprisingly, the study found fruit consumption was not associated with cognitive change.
“This was unanticipated and raises several questions,” said Morris. “It may be due to vegetables containing high amounts of vitamin E, which helps lowers the risk of cognitive decline. Vegetables, but not fruits, are also typically consumed with added fats such as salad dressings, and fats increase the absorption of vitamin E. Further study is required to understand why fruit is not associated with cognitive change.”
Morris says the study's findings can be used to simplify public health messages by saying people should eat more or less of foods in a specific food group, not necessarily more or less of individual foods.

Brain's Natural Anti-Oxidant Defense For Alzheimer's

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Scientists at Dana-Farber Cancer Institute report they have found how the brain turns on a system designed to protect its nerve cells from toxic "free radicals," a waste product of cell metabolism that has been implicated in some degenerative brain diseases, heart attacks, strokes, cancer, and aging.
Potentially, the researchers say, it may be possible to use drugs to strengthen the anti-oxidant system in the brain as a treatment for presently incurable diseases like Parkinson's, Huntington's, and Alzheimer's and possibly other maladies.
Dana-Farber's Bruce Spiegelman, PhD, and colleagues, using a mouse model, discovered that a regulatory protein, PGC-1a, switches on the anti-oxidant system when free radicals, or reactive oxygen species, begin to accumulate. It's believed that some brain diseases involve a failure of the protective system, and the authors report that turning on PGC-1a to high levels in cultured cells protected them against nerve toxins. The findings will be reported in the Oct. 20 issue of the journal Cell.
"This could have broad implications for the many diseases in which reactive oxygen species are implicated," said Spiegelman. Anti-oxidant supplements have been used with some success in patients with neurodegenerative diseases, but Spiegelman noted that the process sparked by PGC-1a "is how nature does it."
Researchers currently are screening drugs in search of compounds that could spur PGC-1a expression in brain cells, as well as exploring whether any harmful side effects might result. PGC-1a is a transcriptional co-activator discovered in Spiegelman's Dana-Farber laboratory in 1998. It has subsequently been found to play a master regulatory role in metabolic processes and muscle function, as well as being a culprit in diabetes.
The report establishes for the first time that PGC-1a both drives the mitochondria to make energy and triggers the cleanup of toxic free radicals that accumulate in the cell as byproducts. As excess free radicals build up, their toxicity places the cell under "oxidative stress," which prompts the cell to produce more PGC-1a, which in turn spurs the anti-oxidant defenses into action.
"With this mechanism, the body can speed up mitochondrial formation and at the same time suppress the creation of reactive oxygen species, which are known to be terribly damaging to the cell," explains Spiegelman, who is also a professor of cell biology at Harvard Medical School. In this respect, the cell could be compared to a self-cleaning oven -- but one that becomes less efficient with age and in certain diseases.
Therefore, the new finding of a specific regulator of the body's own anti-oxidant system could lead to more-effective treatments for a number of diseases, and might even retard some of the effects of aging, the researchers say.

A break in the chain

How Alzheimer's alters a victim's brain -- and life
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In the final stages, Alzheimer's disease turns a grown man or woman into a baby, curled in a fetal position, requiring all the care that a newborn would: feeding, massage, rocking and comforting. But while babies are just opening up to the possibilities of the world, those with Alzheimer's are shutting down, unaware of the joys and sorrows of their external environment.
If you were able to look at their brain, it would appear dramatically shrunken and ravaged: the cerebral cortex -- the outer surface of the brain responsible for all intellectual functioning -- has atrophied; almost every region of the brain is clogged by beta-amyloid plaques and neurofibrillary tangles, making it impossible for nerve cells to communicate with each other.
Alzheimer's disease is named for Alois Alzheimer, a German who 100 years ago first described the ravages of the disease. He cut away the tops of skulls from people who died of a strange, mind-destroying illness that had left them helpless and speechless. He is believed to have been the first person to see inside a diseased brain and view the sticky amyloid plaques and the twisted, hair-like threads of the neurofibrillary tangles.
It's these plaques and tangles that are the hallmark of Alzheimer's disease.
They disrupt the three processes that keep neurons healthy: communication, metabolism and repair. This disruption causes certain nerve cells in the brain to stop working, lose connections with other nerve cells and, finally, die. The destruction and death of nerve cells cause the memory failure, personality changes, problems in carrying out daily activities and other features of the disease.
Even today, the only way to conclusively diagnose Alzheimer's disease is with an autopsy, in the way that Alois Alzheimer did a century ago.
The plaques are spherical structures, sometimes described as tiny "Brillo pads," that contain protein, nerve-cell fragments and other cells. The plaques are made of beta amyloid, a protein fragment snipped from a larger protein called amyloid precursor protein. These fragments clump together outside the nerve cells to form plaques.
The neurofibrillary tangles, found inside nerve cells, look like twisted bits of dental floss. They occur when another protein, called tau, which normally channels chemical messages inside nerve cells, deforms and collapses. This disables the neuron's transport system.
Scientists also still don't know if the plaques and tangles cause the disease or if they are a byproduct of the disease process.
Are they a result of a genetic mutation or caused by an environmental trigger? In Losing My Mind, American journalist Thomas DeBaggio wrote of early onset Alzheimer's, a disease that he said "silently hollows the brain" and slowly "gobbles memory and destroys life."
In it, DeBaggio mused about its potential causes. "The disease, or its potential, appears to rest secretly inside us until its evil time arises and a languid torture begins. This is a disease probably not caused by something you did to your body. It is, most likely, a consequence of bad luck, subtle effects activated in the brain, and parents who carried corrupted genes."

Steps for a cure

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In order to raise money and awareness for Alzheimer’s, 75 walkers took part in the fifth annual Waxahachie Memory Walk early Saturday morning at Getzendaner Park.
“We continue to grow every year,” Bryant Martin, director of public relations for the Greater Dallas Alzheimer’s chapter said. “We have an increase of participants every year.”
The annual walk is based on pledges received by participants and this year the walk raised $11,000.
“This is a time to come together and talk about Alzheimer’s and share ideas about care and research,” Martin said.
Along with the walk which started promptly at 9:30 a.m., bounce houses were available for children and several antique cars were on display for participants.
The Waxahachie Chick-Fil-A also donated 15 percent of their daily receipts on Saturday to the organization.“We serve 46 counties in the Greater Dallas area,” Martin said. “We hold three memory walks during the year, a long with a celebration on Nov. 4 at the Dallas Zoo. The event at the zoo is much larger and this year Terrell Owens is our honorary chairman for the event.”
The event is free and the public is invited.
Alzheimer’s is a neurological brain disease that leaves patients virtually incapable of caring for themselves.
“Alzheimer’s patients tend to lose their good judgments, memory and have a tendency to wander away from their homes,” Martin said. “When people start seeing changes in behavior or short term memory loss in themselves or a loved one, we encourage them to contact our chapter and visit with a doctor. Alzheimer’s begins to develop around the age of 65 but people as young as 35 can develop the disease as well.”
With a large population of baby boomers nearing retirement age, Martin said the Alzheimer’s association is concerned the disease will bankrupt Medicaid and Social Security.
“Our chapter is the only chapter in the country that has pledged $2 million to Alzheimer’s research,” Martin said. “The money goes to finding a cure for Alzheimer’s but the great thing about today’s walk is that the money all stays in Ellis County.”
Nearly 8,000 residents in Ellis County live with some stage of Alzheimer’s.
More than 450,000 Texans and 4.5 million American’s live with the disease as well.
On average, 986 new patients are diagnosed with Alzheimer’s every day.

For a number of walkers on Saturday, their personal ties to Alzheimer’s patients led them to get involved.
“There are several things that led me to support the Alzheimer’s association and the memory walk,” walker Chuck Smith said. “I’ve worked with a hospice for the last five years and watched folks who have been touched by this disease. I’m also good friends with Beverly Worthington who helped start the Memory Walk a year after her husband died from the disease. This is just good for the community as well as the care givers.”
With online pledging and donations, Smith said it’s easy for him to gather support from friends and family members with e-mails sent from home.
“Awareness is the biggest challenge when you’re dealing with something like this,” Smith said. “Lots of people and organizations are fighting for everyone’s attention and the less you understand about the disease the harder it is to support it. But there remains a tremendous need. In the Dallas, Fort Worth and Ellis County area nearly 45,000 people live with Alzheimer’s. Add a caregiver or two to that number and you have a huge number of people who are affected by this disease.”
Smith said people should log on to the Alzheimer’s Association’s Web site and educate themselves, donate and then “put on some walking shoes and come walk with us.”

Research suggests a toke a day may keep Alzheimer's away

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Evidence suggests that people who regularly smoked marijuana in the 1960s and 1970s rarely develop Alzheimer's disease, said Wenk, adding that researchers are eager to develop a drug with the anti-inflammatory properties of marijuana, but without the drug's psychoactive effects.
Researchers at the Scripps Research Institute in La Jolla, California, have found that the active ingredient in marijuana may prevent the progression of Alzheimer’s disease. Their study, recently published in the journal Molecular Pharmaceutics, revealed that THC inhibits an enzyme called AChE—which acts as a “molecular chaperone” to facilitate the formation of amyloid plaque, a substance that forms in the brains of Alzheimer’s patients.
“While we are certainly not advocating the use of illegal drugs,” noted Scripps in their press release, “these findings offer convincing evidence that THC possesses remarkable inhibitory qualities.”
Worldwide, the cost of treating the nearly 28 million people with Alzheimer’s and dementia is $248 billion, according to the Stockholm Gerontology Research Center and the Aging Research Center at Karolinska Instituet. Although there are now 27 drugs in development for Alzheimer’s, there is no effective treatment to cure, modify, or prevent the neurodegeneration caused by the disease—at least, not yet.
Athenagen, a privately held biopharmaceutical company based in South San Francisco, California, has two drugs in development to treat Alzheimer’s. Last month the company raised $50 million in a Series B round, led by Sanderling Ventures of San Mateo, California. “Sanderling is interested in building companies that have big portfolios and can be real, stand-alone, important companies,” Sanderling Managing Director Robert McNeil explains. “Athenagen has that potential.”
The company has two products for treating Alzheimer’s in the pipeline. One is a tablet that improves cognition and enhances memory by targeting a pathway stimulated by nicotine. Early-stage trials in humans are underway.
Athenagen is also advancing its proprietary beta-secretase inhibitor drug, ATG-Z1. “This could be the first compound to actually slow down or even halt the progression of Alzheimer’s,” says Athenagen CEO Scott Harkonen. The drug blocks formation of a protein called A-beta which is toxic to nerve cells. It is also essential to formation of plaques found in Alzheimer’s patients.
The need for a drug that can modify Alzheimer’s is so acute that all 20 of the world’s top pharma companies are targeting the disease. If all goes well, Athenagen’s drug could be available in five years. “The market for a drug like this is akin to the statin drugs that have made such an impact on heart disease,” Dr. Harkonen asserts. “It’s of that magnitude.”

New Alzheimer's Clinical Trials

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The Alzheimer's Disease Cooperative Study (ADCS), a federally-established consortium conducting clinical trials on Alzheimer's disease (AD), will receive $52 million over six years to conduct several new trials, the National Institutes of Health (NIH) has announced. The award is a cooperative agreement between the NIH's National Institute on Aging (NIA) and the University of California, San Diego (UCSD), which coordinates the consortium of nearly 70 sites in the United States and Canada.
The purpose of the award is to test drugs for their effectiveness in slowing down the progression or treating the symptoms of AD, as well as to investigate new methods for conducting dementia research. Specifically, researchers will focus on possible therapies aimed at affecting the beta amyloid peptide and the tau protein, both involved in the development of AD.
"We have learned a great deal from basic and observational research about how Alzheimer's and other neurodegenerative diseases develop," says Richard J. Hodes, M.D., Director of the NIA. "The consortium's work will translate this knowledge in clinical trials of interventions that target the mechanisms underlying Alzheimer's disease."

Among the new studies to be undertaken are:
Docosahexaenoic Acid (DHA) - This trial will examine whether treatment with DHA, an omega-3 fatty acid found in fish, will slow decline in AD. Observational studies associate high fish consumption with reduced risk of AD in people, and studies in mouse models of AD show that dietary DHA reduces brain levels of beta amyloid, oxidative damage associated with beta amyloid, and neurotoxicity.
Intravenous Immunoglobulin (IVIg) - There is increased interest in passive immunization strategies against AD. IVIg contains naturally-occurring antibodies against beta amyloid, and preliminary studies have shown that IVIg may improve cognition. In addition, research has demonstrated that IVIg increased levels of anti-beta amyloid antibodies in plasma and promoted clearance of beta amyloid from cerebrospinal fluid. The new ADCS trial will more definitively demonstrate whether IVIg is useful clinically for treating AD.
Lithium - The biological activity of lithium, which has been shown in animal models to block abnormal changes in tau, has created interest in lithium as a novel treatment for AD. ADCS investigators will undertake a pilot biomarker study to see whether the drug can lower tau and beta amyloid levels in cerebrospinal fluid and be safely tolerated in older AD patients.
Home-Based Assessment - Older individuals, particularly the very elderly, may have physical, social and health limitations that make it difficult for them to take part in research trials. This study, conducted in people aged 75 and older, will examine the use of mail-in questionnaires, automated telephone technology and computerized data collection to assess cognitive, functional, and other factors in the home environment to see how home-based assessments might be used in primary prevention trials. Such an approach could significantly reduce the cost and increase the feasibility of participation in these long-term, costly clinical trials.

These projects join ongoing ADCS trials testing whether statins and high-dose folate/B6/B12 supplements can slow the clinical signs of AD, as well as a study of valproate to determine whether this drug can either slow decline or help delay the agitation and psychosis that often emerge in AD patients.

Leon Thal, M.D., chair of the Department of Neurosciences at the UCSD School of Medicine and principal investigator of the ADCS, notes that the selection of compounds for testing was enhanced by seeking ideas from the biotechnology sector as well as from individual investigators and the consortium's members. "We have been able to bring together a larger universe of people studying therapies for Alzheimer's, and I think this group of studies reflects new thinking in how to approach the disease," he says.

This ADCS consortium was first established in 1991 as an infrastructure of leading researchers to carry out clinical trials for promising new therapies for AD. Investigators have tested such compounds as vitamin E, the anti-Parkinson's disease drug selegiline, estrogen, anti-inflammatories and donepezil for their potential in slowing down or preventing cognitive impairment and/or dementia. Recently, positive but limited effects have been shown in slowing the development of dementia with donepezil.

To date, approximately 4,600 people have participated in the ADCS studies. Neil Buckholtz, Ph.D., who leads the federal government's partnership with the consortium as chief of the Dementias of Aging Branch of the NIA, recognized the efforts of the study participants and their families. "Participating in research takes time and dedication, and the efforts of the participants and their families stand out," Buckholtz notes. "We are deeply grateful for their help in finding new and better ways to treat and prevent Alzheimer's disease." As the new round of trials gets underway, stepped up public participation will be essential for their success, Buckholtz says, and he urges the public to learn more about how to take part in such research. (See information, below)
Alzheimer's disease affects an estimated 4.5 million people in the U.S. It increases dramatically with age, affecting approximately 40-50 percent of people age 85 and older. The numbers of people with AD are expected to rise dramatically with the aging of the population over the next few decades.

Mechanism behind stress leading to Alzheimer’s identified

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That stress causes Alzheimer’s has been known for sometime now, but a recent study on mice has shown why people under stress and anxiety appear more prone to this disease.
Researchers have discovered that stress causes a rapid rise in the brain proteins linked to Alzheimer's disease.
David Holtzman at Washington University in St Louis, Missouri, US, and colleagues placed four-month-old mice in isolation within small spaces. The mice stayed in the confined setting – which causes rodents great stress – for three days or as long as three months.

Findings revealed that only three days of stress caused an abrupt 42% increase in brain proteins that causes the disease.

During the course of the experiment the animals wore a special headset device, known as a micro-dialysis probe, that periodically extracted brain fluid for analysis.

Researchers focused their attention on one molecule in particular - amyloid beta peptide. This molecule is known to contribute to the formation of the amyloid protein tangles and plaques that are the hallmarks of Alzheimer’s disease.
The team found that mice housed in the confined space for three months had nearly twice as much amyloid beta peptide in their brain fluid than the control mice that stayed in regular cages.
“The fact that the effect is so fast is interesting,” said Holtzman. Stress may cause a certain type of brain cell activation that releases amyloid beta peptide, he added.

Rudolph Tanzi at Harvard Medical School in Boston, Massachusetts, US. said that some doctors have observed a possible link between stressful experiences – such as the loss of a spouse – and an older person’s risk of Alzheimer’s disease.(ANI)

Curcumin Complex Helps Clear Brain Plaque

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A curcumin complex extracted from turmeric helped the brain clear amyloid-beta plaque that could otherwise lead to development and progression of Alzheimer's disease and other neurological problems. Researchers from the University of California Los Angeles (UCLA) School of Medicine published their findings in the Oct. 9 issue of the Journal of Alzheimer's Disease (10,2, 2006).

Researchers drew blood taken from six Alzheimer's disease patients and three healthycontrols, and isolated the antigen-fighting macrophages. The isolated immune cells were exposed to the turmeric extract (as Curcumin C3 Complex®, from Sabinsa Corp.) in a cell culture for 24 hours, after which time they introduced amyloid-beta to the culture. The treated macrophages showed improved ingestion of amyloid-beta compared to those not treated with curcuminoids. Macrophages from the healthy controls, which were shown to be effectively clearing amyloid-beta, showed no changes with curcuminoids treatment.

"These initial findings may lead to a new approach in treating Alzheimer's disease by enhancing the natural function of the immune system using curcumin, thus increasing the body's ability to remove plaques that may cause Alzheimer's disease and other forms of dementia," stated UCLA researcher Milan Fiala, M.D. He explained the method researchers used to test the immune cell response of macrophages may provide a novel way of evaluating the effectiveness of drugs in clearing amyloid beta from the brain and may help to individualize Alzheimer's disease treatment.

"The amount of research being conducted on curcuminoids in different and diversified fields of medicine is staggering, and it is becoming evident from results of basic, preclinical and clinical research that they are some of the most promising food derived compounds for managing inflammatory and degenerative conditions," noted Vladimir Badmaev, M.D., Ph.D., vice president of scientific and medical affairs at Sabinsa. "Often in studies, the material being tested is not commercially available. However, our Curcumin C3 Complex is available to manufacturers, as well as to consumers through a variety of finished products."

Stress boosts Alzheimer’s proteins in the brain

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Brief periods of stress can cause a rapid rise in the brain proteins linked to Alzheimer’s disease, according to a study in mice.

Just three days of stress caused an abrupt 42% increase in brain proteins thought to cause the disease. The study helps to shed light on why people who experience great stress and anxiety appear more prone to this illness, experts say.

Researchers placed four-month-old mice in isolation within small spaces one-third the size of normal cages. The mice stayed in the confined setting – which causes rodents great stress – for three days or as long as three months.

During the course of the experiment the animals wore a special headset device, known as a micro-dialysis probe, that periodically extracted brain fluid for analysis.

Human dementia

David Holtzman at Washington University in St Louis, Missouri, US, and colleagues focused their attention on one molecule in particular: amyloid beta peptide. This molecule is known to contribute to the formation of the amyloid protein tangles and plaques that are the hallmarks of Alzheimer’s disease. Previous research has linked higher levels of amyloid beta peptide with increased risk of dementia in humans.

The team found that mice housed in the confined space for three months had nearly twice as much amyloid beta peptide in their brain fluid than the control mice that stayed in regular cages.

Surprisingly, after just three days of living in stressful isolation experimental mice had 42% more amyloid beta peptide in their brain fluid than their control counterparts.

“The fact that the effect is so fast is interesting,” says Holtzman. Stress may cause a certain type of brain cell activation that releases amyloid beta peptide, he says.

Spouse loss

The finding from the mouse study is an “amazing result”, according to Rudolph Tanzi at Harvard Medical School in Boston, Massachusetts, US.

Tanzi says that some doctors have observed a possible link between stressful experiences – such as the loss of a spouse – and an older person’s risk of Alzheimer’s disease.

A previous study of nearly 800 Catholic nuns, priests and brothers found that those plagued by negative emotions, such as depression and anxiety, had about twice the risk of Alzheimer’s as those who took a more laid-back approach to life.

Holtzman says the mouse experiment adds to the growing body of evidence that reducing stress in everyday life might lower a person’s risk of Alzheimer’s disease. He also speculates that anti-anxiety drugs might one day have a role in the control of this illness.

Diet link to Alzheimer's deepens

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A vegetable stir-fry and a glass of red wine might go a long way toward preventing the formation of the brain gunk that can lead to Alzheimer's disease, studies report Monday.
The findings involving experiments with mice add to an increasing body of evidence, including human studies, that suggest the high-fat Western-style diet might lead not just to heart attacks but also to Alzheimer's, a disease expected to afflict up to 16 million people in the USA by 2050.

But if new research by Narayan Bhat of the Medical University of South Carolina and others pans out, Americans might be able to change that future in part by steering clear of artery-clogging foods.

Bhat took healthy lab mice and fed them a diet with lots of saturated fat and cholesterol.

After two months, he gave the mice, which were middle-aged by then, a memory test and found that those fed the bad diet flunked: They made errors finding their way around a water maze.

Mice eating the bad diet also had an increase in a toxic brain protein called beta amyloid, Bhat says. Many scientists believe that beta amyloid deposits in the brain lead to the symptoms of Alzheimer's.

Bhat presented the results on Sunday at the Society for Neuroscience annual meeting in Atlanta. The findings raise the hope that a diet low in saturated fat might prevent that build-up of beta amyloid — and Alzheimer's disease.

A study posted online this month suggests just that: The report in the Archives of Neurology found that people eating a Mediterranean-style diet — low in saturated-fat animal products and high in fruits, vegetables and whole grains — had a lower risk of Alzheimer's than people eating standard American fare.

Italians and others who live around the Mediterranean often drink red wine with dinner, and a second study at the neuroscience meeting adds to evidence suggesting that something in red wine or grapes might offer protection against Alzheimer's.

Giulio Pasinetti of the Mount Sinai School of Medicine in New York gave mice that had been genetically altered to develop Alzheimer's a small dose of red wine every day for 11 months. Then Pasinetti gave a memory test to the wine-fed mice and a control group that received no wine.

The Alzheimer's mice that were given no wine faltered on the test. But the mice that had been drinking small amounts of Cabernet Sauvignon found their way around the maze surely and swiftly, a sign that they still had a sharp memory, Pasinetti says.

Alcohol consumption can cause many health problems. So people who already drink should limit their consumption to about a single glass of red a day, Pasinetti says.

And don't expect wine or any other single food to compensate for a diet that has lots of unhealthful fat, says P. Murali Doraiswamy, an Alzheimer's expert at Duke University: "You can't wash down a double cheeseburger with a glass of red and expect to get a brain benefit."

Structure of enzyme offers treatment clues for Alzheimer's

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Researchers from the University of Chicago and Argonne National Laboratory have deciphered the three-dimensional structure of insulin-degrading enzyme, a promising target for new drugs because it breaks down not only insulin but also the amyloid-beta protein, which has been linked to the cognitive decline of Alzheimer's disease.

This press release issued by EurekAlert says that in the October 19, 2006, issue of Nature (available online Oct. 11), the researchers describe the structures of insulin-degrading enzyme (IDE) in complex with four of the proteins it digests: insulin, amyloid-beta, amylin and glucagon. The structures are exciting because they suggest ways to develop drugs that could either speed up or slow down this ubiquitous enzyme's activity.

"The structure of insulin-degrading enzyme tells us a lot about how it works, which is somewhat unorthodox," said Wei-Jen Tang, Ph.D., associate professor in the Ben May Institute for Cancer Research at the University of Chicago and director of the study. "Understanding how it works gives us clues about how to design drugs either to inhibit or activate it."

"By introducing small, targeted mutations, we have already been able to increase the enzyme's activity by as much as 40-fold," he said. "That gives us a blueprint for the next step, trying to devise a drug that would produce a similar effect."

Ever since I. Arthur Mirsky discovered IDE in 1949, physicians have sought ways to manipulate it. Mirsky thought that by inhibiting the enzyme he could help diabetics by making their insulin remain active longer. More recently, as scientists realized that IDE was also involved in clearance of amyloid-beta, they have begun searching for ways to supercharge the enzyme to see if it could prevent the build-up of the amyloid plaques that are a hallmark of Alzheimer's disease.

Despite more than half a century of intensive research, however, insulin-degrading enzyme has remained "an especially elusive pharmacological target," biochemist Malcolm Leissring of the Scripps Research Institute and neurobiologist Dennis Selkoe of Harvard Medical School wrote in a commentary that accompanies the Nature article.

Using the Advanced Photon Source at Argonne National Laboratory, Tang and colleagues were able to solve the structures of this enzyme in complex with insulin and with amyoid-beta, as well as amylin and glucagon. These "high-resolution crystal structures open the door to the rational design of pharmacological modulators of this important protease," wrote Leissring and Selkoe.

The enzyme, Tang's team reports, resembles the video-game character "Pac-Man," with two bowl-shaped halves joined by a hinge at one end and held closed, most of the time, by a latch of hydrogen bonds on the other end. When the bowls come together, like a shut mouth, they enclose a chamber, shaped like a triangular prism, with a base that measures 35 x 34 x 30 angstroms and a height of 36 angstroms, large enough to contain relatively small peptides, such as insulin or amyloid-beta, which have fewer than 50 amino acids.

Although it can cleave larger molecules, the proteins IDE degrades most readily fit neatly within this chamber. Negative electrical charges on their outer surfaces help to align them with the positive charges on one inner surface of the chamber. Once they are in place, the enzyme slices them multiple times into tiny pieces, which are then discarded.

Although the enzyme's structure is similar to Pac-Man, its behavior differs. Pac-Man keeps his mouth wide open to gobble up anything in his path. With IDE the mouth is usually closed. The hydrogen-bond latch that holds the jaws together protects its active, or catalytic site.

But in a series of experiments, Tang and colleagues were able to make small mutations of IDE that altered only the latch, disrupting the alignment of contacts that normally keep the enzyme closed. Three of these altered versions of wide-open IDE proved to be 30 to 40 times more active than the normal version of the enzyme.

"This suggests that the rate-limiting step may be the speed at which the enzyme can reopen and then clamp down on a new morsel rather than the time it takes to chew something up," said Tang. "This makes us think that if we can slightly alter its shape, we can substantially boost its activity."

The researchers are now searching for small molecules that can duplicate the effects of those mutations, shifting the balance toward the open rather than the closed state. "Such compounds," the authors note, "might facilitate the clearance of amyloid-beta and other pathologically relevant IDE substrates."

"By revealing IDE's active site in unprecedented detail," notes the commentary, "the new structures provided by Tang and coworkers hold great promise for finally realizing Mirsky's dream."

Reduced Risk Of Alzheimer's Disease Associated With Mediterranean Diet
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Eating a Mediterranean diet, which emphasizes fruits, vegetables and olive oil and includes little red meat, is associated with a lower risk for Alzheimer's disease, according to an article posted online that will appear in the December 2006 print issue of Archives of Neurology, one of the JAMA/Archives journals. This association persisted even when researchers considered whether individuals had vascular diseases--diseases of the blood vessels, such as stroke, heart disease and diabetes--suggesting that the diet may work through different pathways to reduce Alzheimer's disease risk.

The Mediterranean diet consists of high amounts of fruits, vegetables, legumes, cereals and fish, mild to moderate amounts of alcohol and low amounts of red meat and dairy products, according to background information in the article. This diet has been associated with a lower risk for several diseases and risk factors, including cancer, obesity, high cholesterol, high blood pressure, problems with processing glucose that may lead to diabetes, coronary heart disease and overall death.

Nikolaos Scarmeas, M.D., and colleagues at Columbia University Medical Center, New York, studied whether the Mediterranean diet could also help prevent Alzheimer's disease--a debilitating neurodegenerative disease--in a group of 1,984 adults with an average age of 76.3. The participants, 194 of whom already had Alzheimer's disease and 1,790 of whom did not, were given complete physical and neurological examinations and a series of tests of brain function. Their diet over the previous year was analyzed and scored based on how closely it adhered to the principles of the Mediterranean diet--scores ranged from zero to nine, with higher scores indicating eating patterns that aligned closely with the Mediterranean diet. The researchers obtained information about vascular disease diagnoses from the exams, participants' or relatives' reports and medical records.

Eating a diet that closely followed the Mediterranean model was associated with a significantly lower risk for Alzheimer's disease. For each additional unit on the diet score, risk for Alzheimer's disease decreased by 19 to 24 percent. After the researchers considered other factors that could influence Alzheimer's disease risk, including age and body mass index, those who were in the top one-third of the diet scores had 68 percent lower odds of having Alzheimer's disease than those in the bottom one-third, and those in the middle-one third had 53 percent lower odds.

Growing evidence links the Mediterranean diet to a reduced risk for vascular disease and suggests that vascular risk factors may contribute to the risk for Alzheimer's disease, the authors write. "Thus, vascular variables are likely to be in the causal pathway between the Mediterranean diet and Alzheimer's disease and should be considered as possible mediators," they continue. "However, when we considered vascular risk factors in our models, the association between the Mediterranean diet and Alzheimer's disease did not change. This was the case despite our attempt to capture vascular comorbidity in the most complete possible way by simultaneously considering both a long list and alternative definitions of vascular variables."

"This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables," the authors conclude.

Mouse antibody for Alzheimer’s
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Stockholm’s Bioarctic Neuroscience has signed an agreement with MRC Technology in London to humanize a mouse antibody under development at Bioarctic for the treatment of Alzheimer’s disease.
MRC Technology’s therapeutic antibody group will use its proprietary humanization technology to generate the humanized clinical candidate.

Bioarctic will pay the London company an upfront fee, development milestones and royalties.

In return, Bioarctic will retain all development and commercialization rights to the antibody. The financial value of the deal was not disclosed.

Bioarctic’s antibody is being developed together with Eisai Japan, a company that developed and markets the drug Aricept for Alzheimer’s disease.

“BioArctic has developed a unique amyloid beta conformational specific antibody (LSAP) for the treatment of Alzheimer’s disease. This antibody targets a newly discovered toxic form of amyloid beta protein called protofibrils that initiates and drives the disease. The antibody will provide an opportunity for early treatment of the disease of significant advantage to the patient,” said Pär Gellerfors, CEO of BioArctic.

Detecting Alzheimer’s
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Could a test to provide early warning for Alzheimer's be on the horizon? As this ScienCentral News video explains, researchers say just such a test is working in animals.
Alarm for Alzheimer's
Researchers at Boston's Brigham and Women's Hospital announced this week that a laser scan for the eyes has so far been 100 percent accurate as an early detector for Alzheimer's disease in mice.
"This is proof-of-concept evidence for early detection. It says that we're on the right track," lead researcher Lee Goldstein says. Goldstein's team used the laser scan eye test to compare mice that were genetically engineered to develop Alzheimer's with normal mice.
The laser scan found beta-amyloid protein in the eyes of the Alzheimer's mice well before any evidence was shown in the brain. In Alzheimer's patients the beta-amyloid protein ultimately builds up into plaques between nerve cells in the brain.
The laser directs a low-intensity beam of light into the lens of the eye, which bounces off of specific particles, similar to how the sun's light bounces off particles of water in clouds. This produces a "scatter pattern," which scientists use to look for beta-amyloid protein in the eye.
According to the National Institute on Aging, Alzheimer's disease affects up to 4.5 million Americans. Alzheimer's patients start to forget loved ones, dates, or how to do simple math. As the disease progresses, Alzheimer's patients can lose the ability to care for themselves and even to speak.
In 2003, Goldstein and others published in The Lancet that the beta-amyloid protein can be found in the eyes of Alzheimer's patients. "This was the first evidence outside of the brain that Alzheimer's was a systemic disorder," he says. "That's important because it allows us to monitor the progression of the disease in parts of the body other than the brain."
Goldstein has also developed another test, which uses eye drops to bind to the beta-amyloid protein. The eye drops contain a chemical which, when combined with the beta-amyloid protein, emits a specific molecular signal when exposed to a laser. Scientists read this molecular fingerprint to figure out precisely where the amyloid protein is located.
Goldstein says that these tests could mean better therapy options for those diagnosed early, potentially decades before lesions form in the brain. "Alzheimer's disease is very difficult to diagnose at any age," he says. "But in order for us to treat this disease we must be able to diagnose it early and intervene early."
Goldstein says the procedure is simple enough that it's similar to other types of eye tests. "The exam itself actually takes less than a second. We do multiple measurements so the whole course of the examination could take a minute or two," he says. "My thinking is that if this pans out for screening, you would want people to be tested by middle age ... part of your annual screening, like a glucose test."

Imaging Sharpens Disease Research
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GE Healthcare, Chalfont St. Giles, UK, is currently developing diagnostic imaging agents for Alzheimer’s disease. Imaging agents that diagnose the presence of beta-amyloid plaque before disease symptoms manifest could potentially enable earlier treatment of the disease with better outcomes. They could also be used to facilitate development of Alzheimer’s drugs.“The whole idea is, if we can measure plaque, then not only can we identify Alzheimer’s patients, but we can also measure the effect of drugs, assuming that the drug effect is intended to reduce plaque,” explains Richard Frank, MD, PhD, vice president of medical and clinical strategy at GE Healthcare. Although drugs would need to demonstrate improvement of Alzheimer’s symptoms to be approved, the ability to see them affect plaque levels would improve decision-making and enable “labeling to include the additional claim of disease modification,” Frank says. Validated Alzheimer’s imaging agents could also be used to improve lead identification and optimization during preclinical development, Frank points out. In the last few years, PET scanners for small animals have become available, he says, which greatly facilitates translation of results from animals to humans.
Last year, the company announced that it will collaborate with Roche, Basel, Switzerland, in clinical trials of Roche’s anti-amyloid drug. Patients will be monitored with GE’s PET imaging agent, Pittsburgh Compound-B (PIB), Frank says. PIB was licensed by GE Healthcare from the University of Pittsburgh in 2003. The collaboration aims to validate the efficacy of both Roche’s anti-amyloid drug and GE’s diagnostic agent. In a separate collaboration, GE Healthcare is working with Eli Lilly, Indianapolis, to further expand GE’s portfolio of beta-amyloid diagnostic agents for Alzheimer’s disease. GE will have access to Lilly’s libraries, and Lilly will be able to utilize diagnostic agents that GE identifies through the partnership. By collaborating on the development of diagnostics and therapeutics for the disease at the same time, the companies hope to realize synergies on both fronts.Earlier this year, the National Institutes of Health launched the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a $60 million, five-year study aiming to attract 800 participants through 58 trial sites located in the U.S. and Canada. “The primary goal is to try to develop and determine the best biomarkers of disease progression in Alzheimer’s disease,” says Susan Molchan, MD, program director for the ADNI project at the National Institute on Aging (NIA). The study will monitor patients using imaging technology, as well as blood, cerebrospinal fluid, and urine sample analysis.Molchan says that all participants in the study will receive serial anatomical MRI scans over a two- to three-year period. About half the participants will also receive FDG-PET scans to measure cerebral glucose metabolism. According to Molchan, prior studies have linked changes in MRI and FDG-PET scans with Alzheimer’s disease progression and risk factors.Initiated by the NIA, the ADNI study involves many federal agencies, pharmaceutical companies, and private non-profit organizations.

CURRIES FIGHT ALZHEIMER'S
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UCLA/VA researchers found that curcumin -- a chemical found in curry and turmeric -- may help the immune system clear the brain of amyloid beta, which form the plaques found in Alzheimer's disease. Published in the Oct. 9 issue of the Journal of Alzheimer's Disease, the early laboratory findings may lead to a new approach in treating Alzheimer's disease by enhancing the natural function of the immune system using curcumin, known for its anti-inflammatory and anti-oxidant properties. Using blood samples from six Alzheimer's disease patients and three healthy control patients, the researchers isolated cells called macrophages, which are the immune system's PacMen that travel through the brain and body, gobbling up waste products, including amyloid beta. The team treated the macrophages with a drug derived from curcumin for 24 hours in a cell culture and then introduced amyloid beta. Treated macrophages from three out of six Alzheimer's disease patients showed improved uptake or ingestion of the waste product compared to the patients' macrophages not treated with curcumin. Macrophages from the healthy controls, which were already effectively clearing amyloid beta, showed no change when curcumin was added. "Curcumin improved ingestion of amyloid beta by immune cells in 50 percent of patients with Alzheimer's disease. These initial findings demonstrate that curcumin may help boost the immune system of specific Alzheimer's disease patients," said Dr. Milan Fiala, study author and a researcher with the David Geffen School of Medicine at UCLA and the VA Greater Los Angeles Health Care System. "We are hopeful that these positive results in a test tube may translate to clinical use, but more studies need to be done before curcumin can be recommended." The patients ranged in age from 65 to 84. Fiala noted that the patients whose immune cells responded were younger and had higher scores on a Mini-Mental State Examination suggesting that curcumin may help those with less advanced dementia. Some of the patients may have already had additional curcumin in their systems due to participation in another UCLA study, which may have impacted findings. "Our next step will be to identify the factors that helped these immune cells respond," said Laura Zhang, a study author and a UCLA/VA research assistant in Fiala's lab. Fiala noted that the method researchers used to test the immune cell response of macrophages may provide a novel way of evaluating the effectiveness of drugs in clearing amyloid beta from the brain and may help to individualize Alzheimer's disease treatment. According to Fiala, macrophages are the soldiers of the innate immune system -- the part of the immune system which is present at birth. Curcumin may support the body's natural immune fighting function in directly helping macrophages clean away amyloid-beta. The treatment of macrophages with curcumin is radically different from some of the vaccine approaches currently being studied.

Marijuana's Key Ingredient Might Fight Alzheimer's
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The active ingredient of marijuana could be considerably better at suppressing the abnormal clumping of malformed proteins that is a hallmark of Alzheimer's than any currently approved drugs prescribed for the treatment of the disease.
Scientists report the finding in the Oct. 2 issue of the journal Molecular Pharmaceutics.
About 4.5 million Americans suffer from Alzheimer's disease, which gradually destroys memory. As more people survive into old age, cases of Alzheimer’s disease are expected to triple over the next 50 years. There is no known cure.
The researchers looked at THC, the compound inside marijuana responsible for its action on the brain. Computer models suggested THC might inhibit an enzyme with the tongue-twisting name of acetylcholinesterase (also called AChE) that is linked with Alzheimer's.
AChE is known to help accelerate the formation of abnormal protein clumps in the brain known as amyloid plaques during Alzheimer's. This enzyme also helps break down the brain chemical acetylcholine, which is linked to memory and learning. Acetylcholine levels are reduced during Alzheimer's.
In lab experiments, the scientists found THC was significantly better at disrupting the abnormal clumping of malformed proteins. THC could completely prevent AChE from forming amyloid plaques, while two drugs approved for use against Alzheimer's, donepezil and tacrine, reduced clumping by only 22 and 7 percent, respectively, at twice the concentration of THC used in the tests.
"We're not advocating smoking dope, but if we can make analogues of THC, it could play a role in treating Alzheimer's," researcher Kim Janda, a chemist at the Scripps Research Institute in La Jolla, Calif., told LiveScience. "It would be nice to do more animal studies along these lines."
Past research on human brain tissues and experiments with rats have suggested that synthetic analogues of THC can reduce the inflammation and prevent the mental decline associated with Alzheimer's disease.
However, marijuana is not necessarily good for the mind. Prior investigations have shown that years of heavy marijuana use, consisting of four or more joints a week, can impair memory, decision making, and the ability to pay attention to more than one thing at a time.

Source: LiveScience.com

Wine, apples, cabbage ward off brain damage, memory loss
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POTATOES, apples, red wine and cabbage all contain substances that act in the same way as drugs used to treat memory loss arising from Alzheimer’s, a reason you must eat them regularly.
They all contain a compound called Resveratrol,that helps to lower levels of the protein material called amyloid-beta peptides that cause the plaques in the brain leading to Alzheimer’s disease, Philippe Marambaud and his colleagues at the Litwin-Zucker Research Centre for the study of Alzheimer’s disease and Memory Disorders said.
Writing in an issue of Journal of Biological Chemistry, they said; “Grape and wines, compared to other plant sources of resveratrol including berries and peanuts, contain more than 600 different components, including well-characterised antioxidant molecules. that work in synergy with small amounts of resveratrol to slow down the progression of the neurodegenerative process in humans.” A Mount Sinai School of Medicine study found giving mice with amyloid plaques red wine slows their memory loss and brain cell death - adding to the body of science linking compounds in the beverage to slowing the Alzheimer’s disease - related symptom.
In the Mount Sinai study, the mice’s wine intake was aligned to what is the equivalent of moderate consumption in humans - a five-ounce glass per day for women and two for men. Is that all? No. Evidences continue to mount suggesting moderate drinking of alcohol could sharpen the mind. The Wake Forest University Baptist Medical Centre in the US researches reported from their study that women aged between 65 and 79 years who consumed between one or two drinks a day, tended to perform better on tests for cognitive function and dementia.
“Women who reported drinking one or more drinks a day had a 40 per cent lower risk of significant declines in learning function over time compared to women who reported no alcohol intake” said lead researcher, Mark Espeland, a professor of Public Health Sciences. Consumption of fruit and vegetable juice may overcome mental ageing and damages too, so confirming some benefit to ageing people. Drinking three glasses of fruit or vegetable juice a week could cut the risk of Alzheimer’s disease by a whopping 75 per cent, Qi Dai wrote in the American Journal of Medicine.
Two apples a day, or a glass or apple juice similarly Prof. Thomas Shea, from the University of Massachusetts Lowell said will keep Alzheimer’s at bay by boosting levels of a neurotransmitter according to results from an animal study. However, “eating and drinking apples and apple juice, in conjunction with a balanced diet, can protect the brain from the effects of oxidative stress - and so we should eat such antioxidant - rich foods,” he said. Although how Alzheimer’s develops is not fully clear , but supports are gathering that the build up of plaque from amyloid deposits are associated with an increase in brain cell damage and death from oxidative stress.
The result of the study which appears to show that the benefits may not be exclusively related to the antioxidant properties of the fruit indicates that apple juice consumption could increase the production of the essential neurotransmitter acetylcholine in the brain, resulting in improved memory. Levels of acetylchloline decrease naturally during ageing, but a substantially bigger drop in acetylcholine levels are associated with Alzheimer’s disease. Indeed, the role of acetylcholine in the brain forms the basis of many medications for Alzheimer’s that seek to increase brain levels of the neurotransmitter to retard mental decline in Alzheimer’s patients.
Calorie-intake cut could also delay the onset of Alzheimer’s disease, found another Mount Sinai School of Medicine study conducted on primates. Its result that suggest healthy eating not only benefits the waistline but also learning functions. The study set for publication in November’s Journal of Alzheimer’s disease, entitled: “Calorie restriction attenuates Alzheimer’s disease type brain amyloidosis in Squirrel monkeys” found that an approximately 30 per cent calorie reduction resulted in reduced Alzheimer’s.
In the study of 8,000 people published in The Lancet Medical Journal, Dr. Monigue Breteler and her colleagues also said a light to moderate drinking cut the risk of dementia by 42 per cent and of vascular dementia, another form of senility, by 70 per cent. What diet can do to reduce the problem of this disease is further substantiated by a study on red cabbage. Red cabbage was seen to reduce the build-up of certain plaques in the brain that could cause Alzheimer’s disease. Its anthocyanins and other polyphenols offer protection against oxidative stress that increases the brain’s chances of cell damage and death.
Writing in the journal LWT - Food Science and Technology, Ho Jin Heo and Chang Yong Lee from Cornell University said additional consumption of vegetables such as red cabbages may be beneficial to increase chemo preventive effects in diseases like Alzheimer’s. Hot on the heels of this is a similar report in the Journal of Science of Food and Agriculture from New Zealand researchers who looked at blackcurrant extracts and Alzheimer’s. Its protective effect was linked to its high anthocyanin content, suggesting the extract could be included in a range of processed functional foods.

Abnormal Protein Linked to Neurological Diseases
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Researchers have identified the abnormal protein common to two devastating neurological diseases -- Lou Gehrig's disease, which causes death by paralysis, and frontotemporal dementia, which starts with bizarre behavior and has a destructive effect on mental function comparable to Alzheimer's disease.
The protein is prosaically designated TDP-43, according to a report in the Oct. 6 issue of Science led by researchers at the University of Pennsylvania School of Medicine. When it folds abnormally, the protein should be quietly removed from the brain. But in some people, the removal system doesn't work, and the protein accumulates inside brain cells. The damage done depends on where the accumulation occurs.
"This provides a beginning of an area of investigation with the goal of trying to turn it into something useful, first as a biomarker and eventually as a target of therapy," said study leader Virginia Lee, director of the university's Center for Neurodegenerative Disease Research.
It has long been thought that the two conditions are somehow related, Lee said. The TDP-43 protein provides the common thread. When its abnormal form accumulates in cells of the frontal and temporal lobes -- the brain areas that control judgment and comportment -- the result is frontotemporal dementia (FTD). When the accumulation is in the spinal cord cells, which control movement, the result is Lou Gehrig's disease, whose formal name is amyotrophic lateral sclerosis, she said.
The incidence of Lou Gehrig's disease is one in 100,000 Americans, Lee said. The incidence of FTD is unknown because it usually is treated as a psychiatric disorder, but it is believed to be the second most common form of dementia, behind Alzheimer's disease.
The researchers used an immunological approach to isolate the protein, Lee said. Their knowledge of other abnormal proteins in neurological diseases, such as beta amyloid in Alzheimer's, made them believe it had a high molecular weight and was highly insoluble.
Working with brain tissue from people who had FTD, the researchers got rid of low-molecular-weight, soluble proteins. They injected what was left into mice, whose immune systems generated antibodies against the material. Work with more than 50,000 tissue samples eventually pointed to TDP-43, a finding confirmed with the use of commercially available antibodies against the protein.
Research yet to be done will focus on why the protein becomes abnormal in the first place and why the body's disposal system doesn't work properly, Lee said.
Stephen Snyder is a program director in the Neuroscience and Neuropsychology of Aging Program at the National Institute on Aging, which funded the new work. "This paper shows a signature protein," he said. "This is exactly the kind of finding that moves us ahead quickly."
But "quickly" has a distinct meaning in the study of neurological diseases, Snyder said. It has been a quarter century since the role of beta amyloid in Alzheimer's disease was discovered, yet work to develop treatments for the disorder is still under way, he said.
"The neurodegenerative-disease nut cracks open grudgingly," Snyder said. "But all that we have learned with Alzheimer's disease will come into play here. The finding of this particular protein in lesions of these different diseases, that has to count for something. It gives us a mechanism involved in these devastating diseases. How it is involved is an interesting thing to look at."

Pomegranate juice protects brain
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A daily glass of antioxidant-rich pomegranate juice could halve the build-up of harmful proteins linked to Alzheimer’s disease, says a new animal study from the USA.
“This study is the first to show beneficial effects (both behavioural and neuropathological) of pomegranate juice in an animal model of AD,” wrote lead researcher Richard Hartman from Loma Linda University in California.
AdvertisementAlzheimer’s disease is the most common form of dementia and currently affects over 13 million people worldwide.
Although the mechanism of Alzheimer’s is not clear, more support is gathering for the build-up of plaque from beta-amyloid deposits. The deposits are associated with an increase in brain cell damage and death from oxidative stress.
It is against the oxidative stress that the polyphenols appear to offer protection.
How the study was conductedHartman and his co-workers supplemented the diets of transgenic mice (APPsw/Tg2576) with pomegranate juice. This strain of mice are engineered to express an amyloid precursor protein (APP) that leads to an early onset of neurological degeneration and subsequently Alzheimer’s disease.
Between the ages of six and 12,5 months, the mice were divided into two groups and received either plain water or a pomegranate juice (PJ) made from concentrate (PomWonderful) diluted 1:160 or 1:80. “Since the PJ concentrate is four times more concentrated than regular strength PJ sold commercially, the dilutions of concentrate are approximately equivalent to dilutions of 1:40 or 1:20 of non-concentrated PJ,” explained Hartman.
Cognitive function was evaluated by subjecting the mice to a water maze task, which required the animal to swim and find a submerged platform in a pool of water. As performance improves, the time decreases for the mouse to escape the maze and the distance swum.
The mice given the pomegranate juice drink were found to negotiate the maze significantly quicker (about 35 percent) and swam a more direct path (on average 3750cm less) than the non-supplemented group, reported the authors in the Elsevier journal Neurobiology of Disease (doi: 10.1016/j.nbd.2006.08.006).
When the researchers examined the quantity of beta-amyloid deposits in the brain cortex of the mice, it was found that the pomegranate juice-supplemented groups had 50 percent less of the protein than the non-supplemented group.
More study neededBeing the first study into the potential protective role of pomegranate concentrate and the antioxidant polyphenols contained within, significantly more study is needed.
The data is based on pomegranate concentrate and no attempt was made by the authors to discriminate the potentially ‘active’ biochemicals in the fruit that may offer protection independently or synergistically, although they said the evidence suggests a complimentary effect of the polyphenols.
“The vast number of compounds in PJ, along with the evidence that these compounds may act together in a synergistic fashion, suggests that isolated components of pomegranate may not be as effective as dietary supplementation with either the whole fruit or its juice,” said the researchers.
“These results suggest that further studies to validate and determine the mechanism of these effects, as well as whether substances in PJ may be useful in Alzheimer’s Disease, should be considered,” they concluded.
Magic ingredient: polyphenolsThe work follows a recent epidemiological study into the possible role of fruit and vegetable juices reducing the risk of Alzheimer’s (The American Journal of Medicine, Vol. 119, pp. 751-759), a result that was also linked to the polyphenol, rather than the vitamin content of the fruit and vegetables.
The researchers from the Vanderbilt University Medical Center found that people drinking juices three or more times per week were 76 percent less likely to develop signs of Alzheimer’s disease than those who drank less than one serving per week. This was after taking into account dietary intake of vitamins E, C and beta-carotene. - (Decision News Media, October 2006)