Hybrid molecules promise for treating Alzheimer's

( new molecular tools that can be used to investigate the process )

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One of the many mysteries of Alzheimer's disease is how protein-like snippets called amyloid-beta peptides, which clump together to form plaques in the brain, may cause cell death, leading to the disease's devastating symptoms of memory loss and other mental difficulties.

In order to answer that key question and develop new approaches to preventing the damage, scientists must first understand how amyloid-beta forms the telltale clumps.

University of Michigan researchers have developed new molecular tools that can be used to investigate the process. The molecules also hold promise in Alzheimer's disease treatment. The research, led by assistant professor Mi Hee Lim, was published online this week in the Journal of the American Chemical Society.

Though the exact mechanism for amyloid-beta clump formation isn't known, scientists do know that copper and zinc ions are somehow involved, not only in the aggregation process, but apparently also in the resulting injury. Copper, in particular, has been implicated in generating reactive oxygen species, which can cause cell damage.

One way of studying the role of metals in the process is by sopping up the metal ions with molecules called chelators and then seeing what happens when the metal ions are out of the picture. When other scientists have done this they've found that chelators, by removing metals, hamper both amyloid beta clumping and the production of those harmful reactive oxygen species, suggesting that chelators could be useful in treating Alzheimer's disease.

However, most known chelators can't cross the blood-brain barrier, the barricade of cells that separates brain tissue from circulating blood, protecting the brain from harmful substances in the bloodstream. What's more, most chelators aren't precise enough to target only the metal ions in amyloid-beta; they're just as likely to grab and disable metals performing vital roles in other biological systems.

Lim and coworkers used a new strategy to develop "bi-functional" small molecules that not only grab metal ions, but also interact with amyloid-beta.

"The idea is simple," said Lim, who has joint appointments in the Department of Chemistry and the Life Sciences Institute. "We found molecules known for amyloid-beta recognition and then attached metal binding sites to them." In collaboration with Ayyalusamy Ramamoorthy, professor of chemistry and associate professor of biophysics, Lim then used NMR spectroscopy to confirm that the new, hybrid molecules still interacted with amyloid-beta.

In experiments in solutions with or without living cells, the researchers showed that the bi-functional molecules were able to regulate copper-induced amyloid-beta aggregation, not only disrupting the formation of clumps, but also breaking up clumps that already had formed. In fact, their molecules performed better than clioquinol, a clinically-available metal chelator that showed promise in early trials with Alzheimer's patients, but has side effects that limit its long-term use.

"Based on their small size and other properties, we believe our compounds will be able to cross the blood-brain barrier, but we want to confirm that using mouse models," Lim said. The researchers also plan experiments to see if their new chelators are as good at preventing and breaking up amyloid-beta plaques in the brains of mice as they are in solutions and cultured cells. ...http://www.eurekalert.org

Huge scope for anti-ageing ingredients

The global anti-ageing food market shows huge potential, with an increasing number, size and variety of companies registering an interest in moving into the sector, claims a new report. ...http://www.nutraingredients.com

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Will olive oil consumption protect from Alzheimer’s?

( phenols such as oleocanthal may have neuroprotective properties )

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"Olive oil could hold key to defeating Alzheimer's," reported the Daily Express. The newspaper reported that a compound found in the oil has been shown to slow down changes in the brain that lead to Alzheimer's disease. According to the paper, researchers believe that the antioxidant that gives the oil its 'peppery bite' will become a key ingredient in new drugs. This laboratory study investigated the effects of an olive oil extract (oleocanthal) on chemicals thought to be involved in Alzheimer’s disease. It found that nerve cells exposed to oleocanthal were better protected from the effects of these potential neurotoxins. However, this study does not indicate that increasing olive oil consumption will protect from Alzheimer’s disease. The olive oil extract and other similar molecules may have a role to play in future development of drugs for Alzheimer’s disease, but these will require considerable further research and development. It will be some time before the direct relevance of these findings to preventing Alzheimer’s are clear, but this is the first step in the process.

Where did the story come from?The research was carried out by Dr Jason Pitt and colleagues from the Northwestern University, the University of Pennsylvania, Western Illinois University and Rutgers University in the US and the Universidade Federal do Rio de Janeiro in Brazil. While the authors provide grant numbers for those that support their research, it is unclear what funding organisations provided these. The study was published in the peer-reviewed medical journal Toxicology and Applied Pharmacology.

What kind of scientific study was this?Alzheimer’s disease is the most common form of dementia, affecting around 420,000 people in the UK. It is a degenerative brain disorder. The exact causes aren’t well understood, but plagues and tangles made of proteins form around brain cells, eventually leading to their damage and death. This causes a range of symptoms that can include confusion, mood swings, poor memory and forgetfulness and more severe symptoms such as delusions or obsessive behaviour.

Research has demonstrated that certain fibres called Aß-derived diffusible ligands (ADDLs) in the brain are the main chemicals responsible for the initiation of Alzheimer’s disease. In this laboratory study, researchers explored the neuroprotective properties of a chemical called oleocanthal, which is derived from olive oil. The researchers prepared ADDLs in the laboratory and investigated the effects of various concentrations of oleocanthal on these molecules. They assessed the effect of this extract on the primary molecules (monomers) that make up the ADDLs and also on the formed ADDLs (which are chains of monomers). They also explored the effects of oleocanthal on nerve cells from the hippocampus, an area in the brain that plays an important role in memory and learning. The hippocampus is one of the areas in the brain affected by Alzheimer’s disease. Previous research has established that ADDLs of a certain size can bind at the synapses (junctions between neurones in the brain) The loss of synaptic function that results is a crucial first step in the development of Alzheimer’s disease.

What were the results of the study?The study found that in the presence of the chemical oleocanthal, the ADDLs became more immunoreactive (i.e. more likely to provoke an immune response) and less soluble (which may lead to a decrease in toxicity). When the chemical was applied to the brain cells, ADDLs formed in the presence of oleocanthal were less likely to bind to the synapses and this was accompanied by reduced deterioration of these cells.

What interpretations did the researchers draw from these results?The researchers say their results suggest that oleocanthal is capable of altering the chemicals implicated in Alzheimer’s disease and can also protect against the effects of these compounds on synapses in the brain. They say that this suggests oleocanthal may be a key compound in the development of treatments for Alzheimer’s disease. What does the NHS Knowledge Service make of this study?Previous research has indicated that phenols (a group of chemical compounds) such as oleocanthal may have neuroprotective properties, and this laboratory study has uncovered some of the complex reactions that may explain these effects. More research is needed to establish exactly how it protects nerve cells, (for example, whether it actually reduces binding at the synapses or whether the protective effect is due to the changes in the structure of ADDLs that it causes).

The researchers report that, overall, their findings are consistent with other studies that have investigated phenolic compounds such as oleocanthal and demonstrated protective effects. This extract from olive oil and other similar molecules may have a role to play in future development of drugs for Alzheimer’s disease, but these will require further research and development. The drug development process is a long one, which starts with studies such as these in the laboratory and later move through animal testing to safety and efficacy studies in humans. While the chemical being tested here - oleocanthal – is an extract from olive oil it has not been tested in humans with Alzheimer’s yet. Also, whether these particular effects will be derived from eating olive oil itself is not clear from these findings. Olive oil is likely to be part of a traditional Mediterranean diet, which is also high in vegetables, fruits and fish, and while there is some evidence that a Mediterranean diet reduces the risk of Alzheimer’s disease it is not clear what specific role olive oil has to play in these benefits. Only further studies can answer these questions. ...http://www.dromoreleader.co.uk

Dairy proteins again linked to blood pressure benefits

A combination of milk proteins may reduce salt-induced increases in blood pressure by about 10 mmHg, according to results of a rat study from Valio. ...http://www.nutraingredients.com

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High blood pressure significantly contribute to Alzheimer's disease

( hypertension could contribute to developing the brain disease )

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Middle-aged adults whose parents have Alzheimer's disease are at increased risk for high blood pressure, evidence of arterial disease and markers of inflammation -- all of which may be associated with later development of Alzheimer's disease.

That's the finding of a study by researchers in the Netherlands who compared 206 adults in 92 families with a parental history of Alzheimer's and 200 adults in 97 families with no parental history of the disease.

The team at the VU University Medical Center in Amsterdam measured the participants' blood pressure, analyzed blood samples for genetic characteristics, cholesterol levels and levels of pro-inflammatory proteins called cytokines, and collected medical history and details about diet, exercise and stress levels.

The study found that 47 percent of adults with Alzheimer's-afflicted parents carried the gene (APOE e4) known to be associated with the disease, compared with 21 percent of those with no family history of Alzheimer's. Those with a family history had higher blood pressure readings, signs of arterial disease and higher levels of several different cytokines.

High blood cholesterol and glucose levels were not associated with parental Alzheimer's disease, according to the study, which is published in the November issue of the journal Archives of General Psychiatry.

"Our study shows that high blood pressure and an innate pro-inflammatory cytokine response in middle age significantly contribute to Alzheimer's disease," wrote Dr. Eric van Exel and colleagues. "As these risk factors cluster in families, it is important to realize that early interventions could prevent late-onset Alzheimer's disease. One could argue for a high-risk prevention strategy by identifying the offspring of patients with Alzheimer's disease, screening them for hypertension and vascular factors and implementing various (non)pharmacological health measures." ...http://www.healthday.com

Low vitamin D again linked to higher mortality

Low blood levels of vitamin D have again been linked to lower survival in the elderly – a study which strengthens calls to confirm if vitamin D supplements could offer protection. ...http://www.nutraingredients.com

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New development in Alzheimer's research

( we give up trying new things )

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Dementias are upon us. The greying of our society is resulting in an increase of those with various dementias because the most significant cause of the condition is growing older. Presently, there are about half a million people in Canada with dementia, and that number is due to increase. One in 11 Canadians over the age of 65 have dementia. Over the next 20 years, it is estimated that the number of those with dementias in North America will increase about 60 per cent.

Statistics have just been released in a major report commissioned by Alzheimer's Disease International (ADI) which is a non-profit located in London, England. For the first time, this report indicates that the numbers of those with dementias are increasing significantly in developed countries, but that an even larger increase in these numbers will come from those in less-developed countries.

There has been a tendency to under-report numbers in the low and middle income countries because there is a stigma associated with brain diseases in these countries. Extended families have been caring for their family members with dementia, but shame has prevented full reporting of the numbers of these patients.

It is now estimated that by 2050 there will be some 115 million people world-wide living with dementia. This number depends on the present situation continuing, that is that there will be no major improvements in either prevention or treatment by that date.

About 60 per cent of those with dementia have Alzheimer's Disease. Other dementias include Parkinson's Disease, and some smaller numbers who have vascular dementia, dementia with Lewy bodies, Creutzfeldt-Jakob disease, etc. Dementias are mainly a result of disease of the brain, but some can be caused by brain injury. Until recently, dementias were all lumped together as senile dementia, which was considered to be a normal part of ageing. It was assumed that nothing could be done about it.

There is still not a cure for dementia, and diagnosis remains difficult, but research in this area is increasing. One of the major recommendations of the ADI report is that research must be accelerated.

One interesting new development in Alzheimer's research is the realization, slowly being reinforced by experiments, that brain activity can be modified as we age. The brain does not of itself cease to learn new things or acquire new skills, we give up trying new things. In addition, exercising both our brains and our bodies may delay the onset of dementia or slow its development. There is even some indication that stimulating our brains with electrodes, or using certain drugs, may have positive results. This leads to the possibility that we may be able to upgrade our cognitive capacities through life.

Caregiving becomes essential for those with dementia. Generally, families are primary care givers. Research indicates that 30 per cent of those with mild dementia, 69 per cent of those with moderate dementia, and 88 per cent of those with severe dementia require care. At the moment, a majority of those in nursing homes are there because they have dementia.

Before institutionalization, however, the main caregiver usually bears the burden of looking after a loved one. In underdeveloped countries, extended families provide care, but the strain still falls, primarily, on one family member.

The effects on the caregiver have been researched. It is estimated that on average 7.4 hours of care per day is required for a dementia patient living at home. Caregivers have been found to be suffering from emotional stress and depression. However, they also report positive reactions because of caring for their loved ones. Companionship, fulfilment and good feelings have been mentioned in interviews. Other research has indicated that those providing care live longer than those who do not do so. It is conjectured that a sense of purpose that comes with giving care is helpful to the caregiver.

I think that enough progress is being made now in brain research that the huge figures projected for those with dementia 30 or 40 years from now will not occur. However, until we get major breakthroughs, we need understanding of this condition and we need good support for those providing care. ...http://telegraphjournal.canadaeast.com

Processed food could have role in depression

People reporting a high consumption of processed foods could be more likely to experience depression in middle age, says a new study that suggests food should play a greater role in preventing depressive disorders. ...http://www.nutraingredients.com

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Mushroom compounds in controlling the development of Alzheimer’s

( organic whole foods that positively impact or help prevent diseases )

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Total Nutraceutical Solutions, Inc. (TNS) (OTCBB:TNUS), announced today that the company has started evaluating several proprietary mushroom compounds for activity in controlling the development of Alzheimer’s Disease (AD). TNS was informed by Model Biosystems, Inc. (MBS), San Clemente, CA, that a recent experiment in Drosophila melanogaster flies (Drosophila) showed that certain TNS proprietary mushrooms had unusual anti-inflammatory activity. MBS was of the opinion that TNS should evaluate these mushroom samples in a special MBS biologic model for Alzheimer’s disease (AD). This proprietary AD model uses a genetic mutant of Drosophila that was developed in the laboratory of Dr. Krishna Bhat, University of Texas, Galveston, Texas. This unique live model system can evaluate the activity of a given compound/ingredient in controlling biologic reactions and compounds that are associated with the development of human AD. The organic whole food mushrooms developed by TNS are being studied, pursuant to a signed research agreement, dated Friday, October 30, 2009, in a double-blinded investigator protocol; the total study will involve over 1,000 Drosophila with 120 organisms in each test group.
Drosophila melanogaster, or fruit-fly is widely used in scientific and medical research. Its importance for human health was recognized by the award of the Nobel Prize for medicine in 1995, for work on the genetic control of early embryonic development. Mutant flies with defects in any of several thousand genes are available, and the entire genome has recently been sequenced. Drosophila helped in the development of drugs to combat pathogens responsible for a range of diseases from skin infections to pneumonia and meningitis. Recent research with fruit-flies has focused on the pathology of Alzheimer’s disease, particularly because of the similarity between human and fly brains and the conservation of the AD genetic pathway.

“The discovery and development of organic whole foods that positively impact or help prevent diseases are welcome breakthroughs in healthcare, as more and more people demand natural alternatives to prevent disease,” stated Marvin S. Hausman MD, CEO, TNS. “We believe that the unique, proprietary technology developed by TNS and used in the production of our natural organic specialty mushrooms, contributes significantly to the potential success of this new Alzheimer’s disease study to be undertaken by TNS and MBS.”

“I am pleased that MBS is able to offer TNS the services of our biotechnology testing in their research and development of natural organic mushrooms for alternative medical approaches to preventing human diseases,” stated Malli Varanasi, President, MBS. “Alzheimer’s disease is a terrible human affliction and new preventative measures would be well-received by all people.” ...http://www.earthtimes.org

Paper proving source of antioxidants for Swiss firm

A Swiss company extracting what it claims are antioxidant polyphenols from pulp and paper processing waste is to scale up the project to offer the product as a functional food ingredient. ...http://www.nutraingredients.com

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Care for your body and your brain

( Because I never stopped )

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"I ask them why I can do it," said the 67-year-old Bruce of Rush, who teaches at Oasis and for MVP Healthcare. "Because that's the only thing I'm paying attention to. Focus, focus, focus. We're so distracted by 16 other things we're doing, we don't pay attention."

You may forget why you walked into a room, but be careful or you'll bang elbows with everyone else scratching their heads wondering why they're there. Boomers and older adults who are seeking ways to keep their faculties may want to remember this — the same active lifestyle and healthy eating habits that keep your body fit can do the same for your mind.

"The absolute most important thing you can do is not have a heart attack," said Dr. Steven Rich, chief of geriatric medicine at Rochester General Health System. "Every cardiovascular risk factor that we've identified to protect against heart disease seems to have an effect against Alzheimer's and other kinds of dementia."

Researchers don't exactly know why a heart-healthy lifestyle benefits the brain. Studies of large numbers of people are showing that those who control high blood pressure and cholesterol, maintain a normal weight, manage their diabetes and get aerobic exercise have a lower risk for dementia. The potential decline in mental abilities and a resulting loss of independence is what may finally convince more people to eat five to nine servings of fruits and vegetables a day and get regular exercise.

"People fear dementia more than death," said Rich. Worry often stems from factors out of a person's control, such as genetics. "It's a relatively small risk," Rich said, "except in patients with lots of family members who had it at a young age. Someone who starts Alzheimer's in their 40s, 50s or early 60s, then your family risk is a little higher." Because family history isn't destiny, geriatricians say the best way to stay sharp is to stay active.Acknowledging there's a balance between maintaining activities and staying safe, Rich said that people should do everything — from keeping the checkbook to making dinner — that they are capable of handling.

Tim Balconi lives that advice. The 51-year-old president of the Unity Health Foundation enrolled in the executive MBA program at the Simon Graduate School of Business at the University of Rochester. He found that reading and studying have improved his memory. While colleagues are amazed that Balconi always comes up with what they need, he said he doesn't have a photographic memory. Instead, he boosts recall by making associations and by careful listening. Let the other person finish speaking before you even plan your response, he said. "You really absorb it. You remember it better."

There's some experimental work into whether active video games, such as Wii, can help improve various aspects of cognition that may transfer to everyday life, said Silvia Sörensen, 48, associate professor in the department of psychiatry at the University of Rochester Medical Center, who has researched cognitive tasks among older adults. At the very least, playing the games can be fun. "The older adults didn't want to give the Wii back," Sorensen said of a pilot study. "We think it's positive."

As for less scientific approaches, try:

Exercise to stay nimble and to help control weight and the risk factors for cardiovascular disease. If you've been inactive or are changing your routine, see your doctor first.

Eat a balanced diet. Consult a registered dietitian for the latest news and guidance. Many products claim to fight the effects of aging, but they may not be regulated by the Food and Drug Administration.

Take up a hobby or take a class. Learning to play an instrument, for example, strengthens connections among neurons in the brain.

The activities are as much for social interaction as brain stimulation.

Dr. Lisa Boyle, 35, an assistant professor in psychiatry at URMC, also works in the memory disorders clinic at the Alzheimer's Disease Care, Research and Education program at Monroe Community Hospital. She said that other things can cause cognitive impairment, so patients are screened for depression, sleep deprivation, other medical conditions and stress. Researchers and practitioners allay fears by saying that dementia isn't forgetting where you put your keys, it's forgetting what keys are for. Often, the remedy is to take a deep breath. "People get frustrated when they can't remember something," said Bruce, the memory teacher. "Forget about it for a little bit. It will come back."Rich, whose patients laughed along with Bob Hope, tells them what the comedian said when asked why he was writing jokes into his 90s. "'Because I never stopped,'" Rich quotes. ...http://www.democratandchronicle.com

Further glucosamine health claim rejected

No causality has been established between glucosamine hydrochloride and a reduced rate of cartilage degeneration in individuals without osteoarthritis, according to an opinion published by EFSA on an Article 14 health claim. ...http://www.nutraingredients.com

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Sleep disturbances in Alzheimer's disease

( sleep is crucial in forming new synaptic connections in the hippocampus )

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A research collaboration led by biologists and neuroscientists at the University of Pennsylvania has found a molecular pathway in the brain that is the cause of cognitive impairment due to sleep deprivation. Just as important, the team believes that the cognitive deficits caused by sleep deprivation, such as an inability to focus, learn or memorize, may be reversible by reducing the concentration of a specific enzyme that builds up in the hippocampus of the brain.

It is known that sleep deprivation can have cognitive consequences, including learning and memory deficits, but the mechanisms by which sleep deprivation affects brain function remain unknown. A particular challenge has been to develop approaches to reverse the impact of sleep deprivation on cognitive function.

The findings, reported in this week's issue of the journal Nature, could present a new approach to treating the memory and learning deficits of insomnia. A molecular mechanism by which brief sleep deprivation alters hippocampal function is now identified in mice, involving the impairment of cyclic-AMP- and protein-kinase-A-dependent forms of synaptic plasticity, or readiness for cognitive function.

Ted Abel, principal investigator and professor of biology in the School of Arts and Sciences at the University of Pennsylvania, led the international team of researchers that found that sleep deprivation in mice affects an important molecular pathway in the hippocampus, a region of the brain known to be important for memory and learning.

The study showed that mice deprived of sleep had increased levels of the enzyme PDE4 and reduced levels of the molecule cAMP, the latter of which is crucial in forming new synaptic connections in the hippocampus, a physiological hallmark of learning.

Researchers then treated the mice with PDE inhibitors, which rescued the sleep deprivation-induced deficits in cAMP signaling, synaptic plasticity and hippocampus dependent memory. This reversal also helped to rescue deficits in synaptic connections in the hippocampus and therefore counteract some of the memory consequences of sleep deprivation.

"Millions of people regularly obtain insufficient sleep," Abel said. "Our work has identified a treatment in mice that can reverse the cognitive impact of sleep deprivation. Further, our work identifies specific molecular changes in neurons caused by sleep deprivation, and future work on this target protein promises to reveal novel therapeutic approaches to treat the cognitive deficits that accompany sleep disturbances seen in sleep apnea, Alzheimer's disease and schizophrenia." ...http://www.medilexicon.com

Folic acid and colon cancer

Supplements of folic acid may reduce the recurrence of colorectal cancer in people with low levels of the nutrient, but not people who already have adequate amounts, says a new study from Harvard. ...http://www.nutraingredients.com

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