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Altered protein involved in a novel link to Alzheimer's disease

New findings of the presence of beta amyloid in the brain of a mouse that overproduces a protein called p25 may help explain the occurrence of sporadic Alzheimer's (as opposed to the less common familial form of the disease) and also why stroke and high blood pressure increase the likelihood of developing Alzheimer's.

Dr. Li-Huei Tsai, a Howard Hughes Medical Institute investigator at Harvard Medical School, presented the latest discovery made possible by her new mouse model for Alzheimer's and other neurodegenerative diseases on June 15 at the annual meeting of the American Society for Biochemistry and Molecular Biology (ASBMB)/8th International Union of Biochemistry and Molecular Biology Conference (IUBMB) in Boston.

Working in collaboration with other labs, the Harvard/Howard Hughes research team is already testing potential compounds to halt, or even prevent, the complex cascade of events caused by the presence of p25 that lead to neurodegeneration. In addition, Dr. Tsai believes their work may suggest an intervention after stroke to lower or prevent additional risk of Alzheimer's. With Dr. Tsai's discovery of beta amyloid in the brain of her mouse model, it is now evident that the overexpression of the p25 protein induces all three pathological features of Alzheimer's disease: beta amyloid plaques (caused by increased Abeta peptides), neurofibrillary tangles caused by hyperphosphorylation of tau, and brain atrophy/loss of neurons. Only low levels of the protein P25 are found in healthy brains. However, in the brains of people with Alzheimer's, the p25 proteins are significantly increased.

P25 is actually a fragment of another protein, and can be formed when a stroke or some other unknown event causes the parent protein, p35, to break. But the newly created p25 behaves very differently from the protein from which it was carved out, says Dr. Tsai. Unlike its shorter-lived parent, p25 keeps accumulating in the brain.
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Contact: Sarah Goodwin
asbmb04@bellsouth.net
770-270-0989
Federation of American Societies for Experimental Biology
14-Jun-2004


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