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Neuronal 'traffic jam' marks early Alzheimer's disease

Early Alzheimer's disease may be precipitated by a "traffic jam" within neurons that causes swelling and prevents proper transport of proteins and structures in the cells, according to new studies by Howard Hughes Medical Institute researchers.

In mouse models of Alzheimer's disease and in human brain samples from people with the disease, researchers observed a characteristic breakdown in neurons that appears to prevent the normal movement of critical proteins to the communications centers of the nerve cells. In a vicious cycle, the traffic jam also could increase production of an abnormal protein that clogs neurons, leading to their failure and eventual death.

The researchers said their findings could provide information that might be used to develop drugs to preserve the molecular transport system and thus the viability of brain cells otherwise lost in Alzheimer's. The findings also could ultimately lead to distinctive markers of early Alzheimer's disease that could be used in early diagnostic tests for the disorder, they said.

The research team led by Lawrence S. B. Goldstein, a Howard Hughes Medical Institute investigator at the University of California, San Diego (UCSD), reported their findings in the February 25, 2005, issue of the journal Science. Goldstein and his colleagues at UCSD collaborated on the studies with a researcher at the Albert Einstein College of Medicine.

According to Goldstein, there has been evidence that late-stage Alzheimer's disease involves a failure of the machinery that transports proteins within neurons. In studies with fruit flies, Goldstein and others had observed that overexpression of the gene for a key protein that underlies Alzheimer's pathology, called beta amyloid precursor protein (beta-APP), triggers defects in axonal transport. A defective version of beta-APP is cleaved to form an aberrant form of amyloid beta (A-beta) peptide that makes up the plaques that surround the neurons of
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
24-Feb-2005


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