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Researchers find association between abnormal tau and damaged brain cell DNA

Scientists have identified a possible cellular mechanism triggered by oxidative stress and DNA damage that is linked to tau, a protein commonly seen in the brains of people with Alzheimer’s disease and certain other neurodegenerative diseases called “tauopathies.” The effect was observed in fruit fly and mouse tauopathy models and in human Alzheimer’s brains.

The laboratory study, led by researchers at Brigham and Women’s Hospital and Harvard Medical School in Boston, and supported in part by NIA, was published online January 26 in Nature Neuroscience. The research suggested a novel pathway in tauopathies by which oxidative stress may lead to a change in chromatin, a complex of DNA and proteins that is found in the nucleus of a cell, that is not seen in the normal aging brain. The analysis indicated that the way genes are expressed in Alzheimer’s brains because of this change in chromatin is consistent with a shift toward a less mature genetic state.

The data identified chromatin as a potential therapeutic target in Alzheimer’s disease and suggested one mechanism by which changes in chromatin are associated with aberrant gene expression, and, ultimately, neurodegeneration in tau-related brain disorders. Further research may reveal additional mechanisms.

Reference: Frost B, et al. Tau promotes neurodegeneration through global chromatin relaxation. Nature Neuroscience, published online Jan. 26, 2014; DOI: 10.1038/nn.3639.