Study suggests role of inflammation in brain disease is complicated
From the WashU Newsroom…
Scientists drilling down to the molecular roots of Alzheimer’s disease have encountered a good news/bad news scenario. A major player is a gene called TREM2, mutations of which can substantially raise a person’s risk of the disease. The bad news is that in the early stages of the disease, high-risk TREM2 variants can hobble the immune system’s ability to protect the brain from amyloid beta, a key protein associated with Alzheimer’s.
The good news, however, according to researchers at Washington University School of Medicine in St. Louis, is that later in the disease, when the brain is dotted with toxic tangles of another Alzheimer’s protein known as tau, the absence of TREM2 protein seems to protect the brain from damage. Mice without TREM2 suffer much less brain damage than those with it.
The findings potentially make targeting the TREM2 protein as a means of preventing or treating the devastating neurodegenerative disease a little more complicated, and suggest that doctors may want to activate TREM2 early in the disease and tamp it down later.
“People in the Alzheimer’s field have already been trying to develop ways to target TREM2,” said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “Now that we have this data, the question is, ‘What does one really want to do? Stimulate it or inhibit it?’”
The study is published online the week of Oct. 9 in Proceedings of the National Academy of Sciences.