The UK's largest medical research charity

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The genetics underlying late-onset Alzheimer's disease could soon be revealed thanks to a collaboration of leading UK experts. The team, led by scientists at Cardiff University, has received 1.3 million pounds from the Wellcome Trust, the UK's largest medical research charity, to scan the entire human genome in search of the genes that predispose people to or protect them from developing the disease.

According to the Alzheimer's Research Trust, there are over 700,000 people currently living in the UK with dementia, of which Alzheimer's is the most common form. This figure is expected to double within the next twenty years. Yet currently, only £11 is spent on UK research into Alzheimer's for every person affected by the disease, compared to £289 for cancer patients.

Now, a team led by Professor Julie Williams from Cardiff University will use a technique known as "genome-wide association scanning" to analyse DNA samples taken from 14,000 people -- 6,000 with late-onset Alzheimer's disease and 8,000 healthy "control" samples from the UK and US -- to identify common genetic variations that increase the risk of the disease. "Alzheimer's is a genetically-complicated story involving many genes, so we need large sample sizes to make sure any genetic links that we find are not mere coincidence," says Professor Williams. "With access to 14,000 DNA samples, our study is the largest genetic study ever to look at Alzheimer's and will undoubtedly produce some valuable insights into what causes this devastating illness. It's very likely that we will find some unexpected associations. We know already that certain genes are involved in more than one form of dementia and that even genes that affect cholesterol level can be a risk factor for Alzheimer's. We need to build a complete picture of the different pathways that lead to the disease. With this knowledge, we should, in time, be able to derive tangible clinical benefits."

Genome-wide association scanning is a powerful technique involving studying 500,000 genetic markers across the human genome. Work on genotyping the DNA samples -- in other words, screening for the particular genetic mutations that are linked to Alzheimer's disease -- will be performed by Dr Panos Deloukas's group at the Wellcome Trust Sanger Institute. "Alzheimer's disease is a major burden on our society and this burden will only increase as our population ages," says Professor Richard Morris, Head of Neurosciences and Mental Health at the Wellcome Trust, which is funding the study. "It is essential that we develop our understanding of the underlying causes of the disease, and genome-wide association scans offer a powerful tool to do just this."

"This is an exciting project that could lead to real progress in our understanding of Alzheimer's," said Mrs Wood, Chief Executive of the Alzheimer's Research Trust. "We are delighted to see this research receive such a huge boost after we funded the initial collection of tissues together with the Medical Research Council. "Alzheimer's is a devastating disease which urgently needs more research funding. It is fantastic that the Wellcome Trust is supporting such a significant project that has the potential to improve the lives of the 420,000 people with Alzheimer's in the UK and their families." http://www.sciencedaily.com

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An animal model of Alzheimer disease

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Cells have evolved multiple mechanisms to ensure proper folding, but a number of molecular and biophysical events-such as changes in pH or temperature, mutations, and oxidation-can disrupt a protein's native shape. When polypeptides fail to achieve or maintain their proper conformation, they commonly aggregate into abnormal "amyloid fibril" structures. Amyloid fibrils define a diverse group of degenerative conditions, including amyotrophic lateral sclerosis, prion diseases, and Alzheimer and Parkinson diseases. In Alzheimer disease, the amyloid fibrils are deposited extracellularly; however, in Parkinson and Huntington disease, similar amyloid fibrils accumulate in the cytoplasm and nucleus of the cell respectively. How amyloid formation promotes disease has generated considerable debate, though mounting evidence implicates the early protofibrillar aggregates as the toxic species.

In a new study in the open-access journal PLoS Biology, Leila Luheshi et al. worked with the fruit fly Drosophila to identify the intrinsic determinants of amyloid β (Aβ) pathogenicity in an animal model of Alzheimer disease. (Aβ peptide is a primary component of amyloid plaques in the brains of patients with Alzheimer disease.) Determining how amyloid formation causes disease requires a better understanding of the molecular and biophysical conditions that promote protein aggregation. But such an understanding has proven technically challenging, in part because protein misfolding and aggregation in test tubes can't replicate cellular pathways designed to mitigate the toxic effects of these events. Luheshi et al. circumvented this problem by integrating computational predictions of protein aggregation propensities with in vitro experiments to test the predictions and in vivo mutagenesis experiments to link predicted aggregation propensity with observed neurodegeneration in the flies.

Overall, the researchers found a clear correlation between a variant's predicted tendency to aggregate and its influence on fly longevity. The same relationship was seen between predicted aggregation propensity and locomotion, though a few variants did not follow this pattern. An interesting case presented with a variant (131E/E22G), whose neuronal effects did not match its predicted aggregation propensity. The 131E/E22G peptide aggregated at rates similar to the Alzheimer variant in vitro as well as in the fly brains. But because the 131E/E22G peptide deposits were not accompanied by cavities in brain tissue-a telltale sign of neurodegeneration-the flies showed no neurological deficits.

This finding fits with reports that the density of Aβ plaques in elderly patients with Alzheimer disease does not correlate with the severity of clinical symptoms. Instead, it is the soluble protofibrillar aggregates, not the mature amyloid plaques, that cause neurodegeneration. Recomputing the propensities of each Aβ variant to form these protofibrillar species revealed not only an improved overall correlation with toxicity, but it also brought the previously anomalous 131E/E22G variant in line with the prediction algorithm.

Altogether, these results show that Aβ's toxic effects in a living organism can be predicted based on a computational analysis of its tendency to form protofibrillar aggregates. And even though cells have evolved multiple mechanisms to regulate folding, the researchers argue, it is the intrinsic tendency of the peptide's sequence to aggregate that governs its pathological propensity. Though the researchers focused on the peptide most closely associated with Alzheimer disease, they believe their approach will work for many other diseases as well. http://www.sciencedaily.com

Brown marine algae mined for functional ingredients
Polysaccharides from brown marine algae could provide the ingredients for a new wave of beverages with health benefits, according to researchers in Ireland.

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Benefits for the treatment of Alzheimer's disease

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If you are taking some of the commonly used hypertension (high blood pressure) drugs you might also be significantly lowering you chances of developing Alzheimer's disease and cognitive decline, according to a new study. The study, carried out by scientists at the Mount Sinai Medical Center, indicates that numerous elderly patients who are currently taking anti-hypertensive medications may enjoy additional benefits from their medicines.

Dr. Giulio Maria Pasinetti, Mount Sinai Medical Center, said "If we can deliver certain anti-hypertensive drugs to patients at high risk to develop Alzheimer's disease, at doses that do not affect blood pressure, these drugs could be made available for all members of the geriatric population identified as being at high risk for developing Alzheimer's disease."

Dr. Pasinetti and team have spent the last twenty-four months examining over one thousand drugs to see whether they might have any benefits for the treatment of Alzheimer's disease and dementia. Out of 55 candidate drugs which are prescribed for hypertension, the team has detected 7 promising ones. They found that these drugs are able to prevent the production of beta-amyloid, which causes Alzheimer's disease.

Experiments on mice which were genetically modified to develop Alzheimer's showed that they benefited significantly when given Valsartan, an anti-hypertensive agent. When these mice were given very low doses of Valsartan the production of beta-amyloid was prevented. The following drugs also had a similar effect - Propranolol HCI, Carvedilol, Losartan, Nicardipine HCI, Amiloride HCI and Hydralazine HCI.

The researchers believe this study could lead the way to developing new methods of treating Alzheimer's disease and cognitive deterioration in general. The team says further studies are needed on humans to see whether these anti-hypertensive agents might have the same effect they had on mice. Dr. Pasinetti said "The use of these drugs for their potential anti-Alzheimer's disease role is still highly experimental, and at this stage we have no clinical data beyond phenomenological observation in humans. We need to complete preventive and therapeutic clinical trials in the near future if we are to identify certain anti-hypertensive drugs with anti beta-amyloid antioligomeric activities, which will need to be prescribed at dosages that do not interfere with blood pressure in normotensive Alzheimer's disease patients." http://www.sciencedaily.com

Micro-fibres eyed as future functional ingredients
'Micronised' insoluble fibres, insoluble fibres processed to the micron scale, could favourably change the gut health of hamsters and may translate into important ingredients for functional foods, suggests new research.

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First Alzheimer's Disease Special Needs Plan

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Diseases that cause neurons to break-down, such as Alzheimer's, Multiple Sclerosis and Creutzfeldt-Jakob disease (Mad Cow Disease), continue to be elusive to scientists and resistant to treatments. A new finding from University of Michigan researchers demonstrates an unpredicted link between a virtually unknown signaling molecule and neuron health.

The molecule PI(3,5)P2 is a lipid found in all cells at very low levels. Lipids are a group of small organic compounds. While the best studied lipids are fats, waxes and oils, PI3,5P2 is a member of a unique class of lipids that signal the cell to perform special tasks. PI(3,5)P2 plays a key role in the survival of nervous system cells. "In mice, lowered levels of PI(3,5)P2 leads to profound neurodegeneration," said Weisman. "It suggests that we have a good place to look to find treatments for neurodegenerative diseases such as Alzheimer's."

Weisman, who is also professor of Cell & Developmental Biology at the U-M Medical School and her colleagues, began from clues that were hidden in a conserved genetic pathway in yeast (a pathway that has remained the same in yeast, plants and humans over evolutionary time). Studies in yeast showed that the enzyme that manufactures the lipid is governed by the FIG4 and VAC14 genes, which exist in yeast, mice and humans.

Working with two independently derived mouse models, Weisman's team and collaborators including graduate student Clement Chow and Professor Miriam Meisler of the Department of Human Genetics at the U-M Medical School, reached the same conclusions in a pair of important papers for neuroscience research.

Building on research from Meisler, a mouse geneticist, and Weisman, a yeast geneticist, the collaborators published a paper in Nature, July 5, 2007, showing that in mice, the FIG4 gene is required to maintain normal levels of the signaling lipid and to maintain a normal nervous system. Importantly, they found that human patients with a very minor defect in their FIG4 genes had serious neurological problems. The signaling lipid PI(3,5)P2 (short for phosphatidylinositol 3,5-bisphosphate) is part of a communication cascade that senses changes outside the cell and promotes actions inside the cell to accommodate to the changes.

Weisman's team found that mice missing the VAC14 gene, which encodes a regulator of PI(3,5)P2 levels, suffer massive neurodegeneration that looks nearly identical to the neurodegeneration seen in the FIG4 mutant mice. In both cases the levels of PI(3,5)P2 are one half of the normal levels. The fact that both mice have half the normal levels of the lipid and also have the same neurodegenerative problems provides evidence that there is a direct link between the lipid and neuronal health. The new findings indicate that when Vac14 is removed, the cell bodies of many of the neurons appear to be empty spaces and the brain takes on a spongiform appearance. http://www.sciencedaily.com

Cranberry juice offer anti-viral possibilities - study
Cranberry juice's benefits may even extend to protecting against viruses, according to results of study from New York-based researchers.

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First Alzheimer's Disease Special Needs Plan

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Evercare, one of the nation's, and Arizona's, largest health care coordination programs, today unveiled the details of the first-ever Medicare Advantage Special Needs Plan designed exclusively for people with Alzheimer's disease and chronic dementia. Residents of Maricopa County, Ariz. will be the first in the country to have access to this innovative health plan with tailored benefits and services, including special prescription drug coverage and the Alzheimer's Association Safe Return® program. Evercare Care Managers will collaborate with memory disorder specialists from the prestigious Phoenix-based Banner Alzheimer's Institute, with the goal of enhancing Evercare's innovative model of care.

The Evercare® Health Plan for People with Alzheimer's Disease and Related Dementia provides benefits that go beyond traditional Medicare coverage. It is designed to meet the specific needs of families coping with the stress and issues of Alzheimer's disease and related dementia by providing personalized support from Evercare Care Managers. These trusted partners help guide members through the maze of health care services with the goal of delivering the kind of coordinated care and health outcomes that families have said in surveys gives them peace of mind.

"For the first time, people with Alzheimer's disease and related dementia will be able to obtain health care specifically designed to address their complex health, behavioral and social support needs," says Charles Dow, Regional Executive Director of Evercare Southwest Region and Executive Director of Evercare Arizona. "Evercare is proud to team with Banner Alzheimer's Institute, one of the region's most respected organizations for patients with memory loss and thinking problems. Through our shared focus on innovation and Evercare's legacy of highly personalized health care coordination, we hope to advance the quality care for people with Alzheimer's and their families in Maricopa County."

Specific member benefits include:

- Prescription drug coverage that provides access to prescriptions regularly utilized by people with Alzheimer's disease and chronic dementia (including Aricept®);

- Enrollment in the Alzheimer's Association's Safe Return program, that helps reunite loved ones with the person with dementia who has wandered;

- Care Manager coordination of Alzheimer's disease education, training and end-of-life planning services;

- Bereavement counseling and services to help caregivers cope with their emotions and stress;

- Emergency respite services that provide caregivers with a break so they can address their own health care needs, which are often overlooked due to the demands and stress of caregiving; and

- Access to Banner Alzheimer's Institute's care and treatment programs for those with Alzheimer's and chronic dementia. http://www.sciencedaily.com

Olive extract linked to better brain health
An extract from olive mill wastewater may protect brain cells from oxidative stress and guard against neurodegenerative diseases.

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