Patients with Alzheimer’s disease run a high risk of seizures. While the amyloid-beta protein involved in the development and progression of Alzheimer’s seems the most likely cause for this neuronal hyperactivity, how and why this elevated activity takes place hasn’t yet been explained – until now.
A new study by Tel Aviv University researchers, published in Cell Reports, pinpoints the precise molecular mechanism that may trigger an enhancement of neuronal activity in Alzheimer’s patients, which subsequently damages memory and learning functions. The research team, led by Dr. Inna Slutsky of TAU’s Sackler Faculty of Medicine and Sagol School of Neuroscience, discovered that the amyloid precursor protein (APP), in addition to its well-known role in producing amyloid-beta, also constitutes the receptor for amyloid-beta. According to the study, the binding of amyloid-beta to pairs of APP molecules triggers a signalling cascade, which causes elevated neuronal activity.
Elevated activity in the hippocampus—the area of the brain that controls learning and memory—has been observed in patients with mild cognitive impairment and early stages of Alzheimer’s disease. Hyperactive hippocampal neurons, which precede amyloid plaque formation, have also been observed in mouse models with early onset Alzheimer’s disease.”These are truly exciting results,” said Dr. Slutsky. “Our work suggests that APP molecules, like many other known cell surface receptors, may modulate the transfer of information between neurons.”
With the understanding of this mechanism, the potential for restoring memory and protecting the brain is greatly increased.
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A large and potentially groundbreaking drug trial holds the promise of a new way to treat Alzheimer’s disease, but the test will require thousands of healthy volunteers who may be especially difficult to recruit, in part because of a simple fact about the widely feared illness: Those who have, or are likely to get, Alzheimer’s disease may not want to know it.
The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s, or A4 Study, is the first to try to prevent memory loss by identifying and treating people whose brains show the earliest changes related to the disease, years before they begin to lose cognitive function.
Volunteers aged 65 to 85 will be screened for the presence of amyloid plaque, clumps of a protein found in the fatty membrane surrounding nerve cells, that builds up in the brain as people age and seems to be connected to Alzheimer’s. Researchers hope the drug could significantly curtail the disease, which currently afflicts 5 million Americans and is projected to affect 16 million by 2050.
Over the past two months, researchers at 60 sites across the U.S., Canada and Australia began seeking as many as 10,000 volunteers to be screened for the 39-month trial, which is sponsored by the National Institutes of Health, the pharmaceutical company Ely Lilly & Co., and others.
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More than 5 million Americans suffer from Alzheimer’s disease, the affliction that erodes memory and other mental capacities, but no drugs targeting the disease have been approved by the U.S. Food and Drug Administration since 2003. Now a paper by an MIT professor suggests that a revamped way of financing Alzheimer’s research could spur the development of useful new drugs for the illness.
“We are spending tremendous amounts of resources dealing with this disease, but we don’t have any effective therapies for it,” says Andrew Lo, the Charles E. and Susan T. Harris Professor of Finance and director of the Laboratory for Financial Engineering at the MIT Sloan School of Management. “It really imposes a tremendous burden on society, not just for the afflicted, but also for those who care for them.”
Lo and three co-authors propose creating a public-private partnership that would fund research for a diverse array of drug-discovery projects simultaneously. Such an approach would increase the chances of a therapeutic breakthrough, they say, and the inclusion of public funding would help mitigate the risks and costs of Alzheimer’s research for the private sector.
There would be a long-term public-sector payoff, according to the researchers: Government funding for Alzheimer’s research would pale in comparison to the cost of caring for Alzheimer’s sufferers in public health-care programs. The paper’s model of the new funding approach calls for an outlay of $38.4 billion over 13 years for research; the costs of Medicare and Medicaid support for Alzheimer’s patients in 2014 alone is estimated to be $150 billion.
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