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New enzyme tied to tangles in Alzheimer's disease

Boston, MA - June 22, 1999 -- Opening a new avenue for understanding and perhaps eventually treating Alzheimer's disease, researchers from Boston and New York have identified an enzyme that appears to restore the function of a key player in Alzheimer's disease. The enzyme, known as Pin1, is depleted in brains of people with Alzheimer's disease, according to a paper in the June 24 issue of the weekly journal Nature.

"This is the first study to show a potential role for Pin1 in Alzheimer's disease," says cell biologist and senior author Kun Ping Lu MD PhD, an associate physician at Beth Israel Deaconess Medical Center in Boston and an assistant professor of medicine at Harvard Medical School.

Affecting an estimated 4 million people nationwide, Alzheimer's disease is the most common cause of dementia in older people. The disease disrupts memory, thought and language in the brain by damaging synapses and killing nerve cells. Abnormal clumps called plaques and tangled bundles of fibers are the two major hallmarks of Alzheimer's. Scientists do not know exactly how these changes relate to the loss of nerve cells and brain atrophy. Plaques can occur in the brain without much change in brain function, but tangles appear to be more directly associated with dementia. Pin1 may play a role in the formation -- or prevention -- of tangles.

The neurofibrillary tangles in Alzheimer's occur inside individual nerve cells. The tangles are largely composed of the long protein tau. Normally, tau's job is assembling and maintaining the microtubules that stretch from one end of the nerve cell to the other. Microtubules keep the long nerve axons healthy from the muscle to the brain by transporting cell nourishment and structural components.

Tau can be derailed from a microtubule when too many phosphates leap on board the tau and change tau's shape. The distorted tau cannot maintain the microtubules. The microtubules fall apart, infering with a ne
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Contact: Carol Morton
cmorton@caregroup.harvard.edu
617-667-4431
Harvard Medical School
24-Jun-1999


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