TREM2

TREM2 (triggering receptor expressed on myeloid cells 2) is a receptor that sits across the cell membrane. In the brain, almost only microglia (the brain's immune cells) carry it. It senses negatively charged lipids, apolipoproteins, and amyloid-beta, the sticky protein that builds up in your brain in Alzheimer's. It then signals through a partner protein, DAP12, to shift microglia from their resting state into a 'disease-associated' (DAM) state. That shift changes how they engulf debris, handle lipids, survive, and wall off plaques. One rare variant, R47H (rs75932628), roughly doubles or triples the risk of late-onset Alzheimer's in pooled analyses. And losing both copies of TREM2 causes Nasu-Hakola disease. Soluble TREM2 in spinal fluid is being explored as a marker of microglial activity. TREM2-activating antibodies even reached clinical trials. But the lead candidate, AL002 (Alector), missed its main goal in the Phase 2 INVOKE-2 trial in early-Alzheimer's patients in late 2024, so that strategy is being rethought. Overall, TREM2 is a key link between innate immunity and amyloid and tau pathology.

Last reviewed: June 22, 2026

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