# 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.

## Sources

- Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al.. (2013). TREM2 variants in Alzheimer's disease. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1211851
- Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al.. (2013). Variant of TREM2 associated with the risk of Alzheimer's disease. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1211103
- Qin Q, Wang M, Yin Y, Tang Y. (2024). A systematic review of the role of TREM2 in Alzheimer's disease. Frontiers in Aging Neuroscience. https://doi.org/10.3389/fnagi.2024.1393809

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_Canonical: https://longevity-switzerland.com/en/glossary/trem2 · Part of Longevity Cities · Updated 2026-06-22_