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Tau Gene Linked To Family Of Neurodegenerative Disorders; Finding May Yield Insight Into Onset Of Alzheimer's Disease

Researchers led by a UC San Francisco neurologist are reporting findings that they say may put them an important step closer to understanding the way in which Alzheimer's disease ravages the brain cells of patients.

In a paper published in the October 27 issue of Proceedings of the National Academy of Sciences, the researchers announce that they have identified three mutations in a gene that produces the tau protein, and have determined that these mutations cause several related hereditary neurodegenerative diseases, the most prevalent known as frontotemporal lobe dementia.

While the finding does not directly implicate the tau gene in Alzheimer's disease, it does so strongly by association, said the senior author of the study, Kirk Wilhelmsen, MD, an assistant professor neurology at UCSF. The tau protein has long been a suspected factor in Alzheimer's disease because abnormal, insoluble, tangled filaments of the protein-are always found in the autopsied brains of people who have the disease. But because researchers have never found a mutation in the tau gene of Alzheimer's patients, they had come to think that the neurofibrillary tangles, composed primarily of tau protein, were but an inconsequential by-product of some other factor that actually caused nerve cell degeneration.

Now that there is hard evidence that tau, itself, is capable of killing brain cells, the picture changes, said Wilhelmsen. "Finding a direct link between mutations in the tau gene and these hereditary neurodegenerative diseases strongly indicates that tau is an important player in neurons dying in Alzheimer's disease and many other diseases, as well," he said.

The goal now, he said, is to figure out what causes tau protein to accumulate in insoluble filaments in the brain cells of Alzheimer's patients. While mutations in tau gene appear to lead directly to cell death in the hereditary diseases studied, Wilhelmsen said he and colleagues don't believe that a tau mutation oc
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Contact: Jennifer O'Brien
jobrien@itsa.ucsf.edu
415-476-2557
University of California - San Francisco
27-Oct-1998


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