AlzForum: ApoE and Trem2 Flip a Microglial Switch in Neurodegenerative Disease

A flurry of recent studies implicating microglia as key players in neurodegenerative diseases, particularly Alzheimer’s, has cued many labs to try to figure out how these cells function in health, and how they change in disease. Adding a piece to the puzzle, scientists led by Oleg Butovsky of Brigham and Women’s Hospital in Boston report in the September 19 issue of Immunity that two genes with variants known to alter Alzheimer’s risk—APOE and TREM2—orchestrate the cells’ passage from a homeostatic state to a disease-associated state, at least in mice.

“This is a fascinating paper. It provides substantial evidence for an APOE-TREM2 pathway in mouse microglia that senses apoptotic neurons and induces a ‘neurodegenerative’ phenotypic switch,” wrote Christopher Glass, University of California, San Diego, in an email to Alzforum.