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Study suggests a second dimension to Alzheimer's disease

The genes responsible for an inherited form of Alzheimer's disease play a direct role within cells that has largely been overlooked, according to a report in the September 8, 2006 issue of the journal Cell, published by Cell Press. The findings suggest that there may be an additional dimension to the irreversible neurodegenerative disorder, which potentially suggests a new avenue for the pursuit of therapies, the researchers said.

The researchers found that two genes mutated in familial Alzheimer's disease known as presenilins may control the balance of calcium within cells by acting as a calcium channel. Calcium is an important signaling molecule, with effects on the nervous system that include functions relevant to learning and memory, the researchers said. The research team also discovered that the mutant forms of presenilin--which have been linked to about 40 percent of familial Alzheimer's disease cases--lose the ability to serve this function.

Presenilins are primarily known for their role as an enzyme that cleaves amyloid precursor protein (APP) to form amyloid -peptide, the principal constituent of the plaques that riddle the brains of Alzheimer's patients.

"Clearly it makes sense that presenilin's role in cleaving APP would affect Alzheimer's disease," said Ilya Bezprozvanny of UT Southwestern Medical Center at Dallas. "But our findings suggest a totally different angle, raising the possibility that presenilin's effect on the disease may be two-fold."

Bezprozvanny cautioned, however, that further work is required to determine whether or not the genes' other role in calcium regulation has a causal connection to the symptoms of Alzheimer's disease.

Alzheimer's disease affects nearly 2% of the population in industrialized countries. Most cases of the disease are of unexplained origin and are characterized by late onset in people over the age of 60. A small fraction of cases are characterized by an earlier onset
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
7-Sep-2006


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