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Calcium may be the key to understanding Alzheimer's disease
Date:7/18/2008

PHILADELPHIA, PA - Researchers at the University of Pennsylvania School of Medicine have shown that mutations in two proteins associated with familial Alzheimer's disease disrupt the flow of calcium ions within neurons. The two proteins, called PS1 and PS2 (presenilin 1 and 2), interact with a calcium release channel in an intracellular cell compartment.

"The 'calcium dysregulation' hypothesis for inherited, early onset familial Alzheimer's disease has been suggested by previous research findings, but our current study identifies a molecular mechanism that makes this hypothesis very compelling," says lead author J. Kevin Foskett, PhD, Professor of Physiology. "Mutated PS1 and PS2 caused exaggerated cellular calcium signaling in cells through a calcium channel in the endoplasmic reticulum called the inositol trisphosphate receptor [InsP3R], suggesting that it or other proteins in this calcium signaling pathway could be targets for new Alzheimer's disease therapies." The study appeared in the June 26 issue of Neuron.

Alzheimer's disease affects as many as 5 million Americans, 5 percent of whom have the familial form. The hallmark of the disease is the accumulation of tangles and plaques of amyloid beta protein in the brain. "The amyloid hypothesis has long been invoked to explain the cause of Alzheimer's" says Foskett. In the Neuron study, cells that carried the disease-causing mutated form of PS1 showed increased processing of amyloid beta that depended on the interaction of the PS proteins with the InsP3R. This observation links mis-regulation of calcium inside cells with the production of amyloid, a characteristic feature in the brains of people with Alzheimer's disease.

Current therapies for Alzheimer's include drugs that treat the symptoms of cognitive loss and dementia. Drugs that address the pathology of Alzheimer's are only experimental. For example, a vaccine that stimulates antibodies to amyloid beta is currently being
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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