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Gladstone study reveals how genetic factor may increase risk for Alzheimer's disease

an abnormal change to the protein tau, which is also heavily affected by Alzheimer's disease. Both apoE4 fragments and Alzheimer's disease lead to the abnormal attachment of phosphate groups on tau that can end up contorting the shape of brain cells.

The investigators suspect that the fragmentation of apoE4 is caused by a neuron-specific enzyme, which they are now trying to identify and block with drugs.

"From this and our previous studies, we believe that the protease that cleaves apoE4 may serve as a therapeutic target for the prevention and treatment of Alzheimer's disease, especially in patients who are impacted by apoE4," said the senior author of the study, Yadong Huang, MD, PhD, staff research investigator at the Gladstone Institute of Neurological Disease (GIND) and assistant professor of pathology at the University of California, San Francisco (UCSF).

"With this work, we're a significant step closer to solving the key riddle of apoE4, namely, what is occurring at the molecular level that makes this protein so active in causing neurodegenerative disease," explained Dr. Robert Mahley, "Research of this kind is essential for the development of better treatments for Alzheimer's disease."


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Contact: John Watson
jwatson@gladstone.ucsf.edu
415-695-3833
University of California - San Francisco
23-Mar-2004


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