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Mechanisms ID'd for Role of TREM2 Mutation in Alzheimer's

Risk allele linked to smaller hippocampal volume, increased p-tau181p, poorer cognitive performance
THURSDAY, Oct. 17 (HealthDay News) -- TREM2 mutation carriers have increased brain tissue loss and other changes typically observed in Alzheimer's disease, according to a letter to the editor published in the Oct. 17 issue of the New England Journal of Medicine.
Using data from 478 older adults (mean age, 75.5 years), who underwent brain magnetic resonance imaging once annually for two years, Priya Rajagopalan, M.B., B.S., M.P.H., from the University of Southern California in Los Angeles, and colleagues examined how a variant in TREM2 affects the risk of Alzheimer's disease by mapping its effects on the brain. The participants included 100 adults with Alzheimer's disease, 221 with mild cognitive impairment, and 157 healthy controls.
The researchers found that, compared with non-TREM2 mutation carriers, carriers lost 1.4 to 3.3 percent more of their brain tissue in a pattern that was similar to the profile of Alzheimer's disease. Compared with healthy elderly people, mutation carriers lost brain tissue twice as quickly. After adjustment for age and sex, the risk allele correlated with smaller hippocampal volumes and increased levels of cerebrospinal fluid biomarker p-tau181p, typically seen in Alzheimer's disease, and with poorer cognitive performance.
"The TREM2 risk variant may affect signaling by TREM2 receptors expressed on microglial cells in the brain," the authors write. "This may affect brain amyloid clearance, leading to Alzheimer's disease-like neurodegeneration and accelerated cognitive decline."
The study was supported by the Alzheimer's Disease Neuroimaging Initiative, which is partially funded by the pharmaceutical industry.
Full Text (http://www.nejm.org/doi/full/10.1056/NEJMc1306509 )
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