reviewMolecular NeurodegenerationApr 17, 2025GOLD OA

TREM2 and sTREM2 in Alzheimer’s disease: from mechanisms to therapies

Xiamen University · Shenzhen University Health Science Center · +4 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor predominantly expressed by microglia in the brain. Recent studies have established TREM2 as a central immune signaling hub in neurodegeneration, where it triggers immune responses upon sensing pathological development and tissue damages. TREM2 binds diverse ligands and activates downstream pathways that regulate microglial phagocytosis, inflammatory responses, and metabolic reprogramming. Interestingly, TREM2 exists both in its membrane-bound form and as a soluble variant (sTREM2), that latter is generated through proteolytic shedding or alternative splicing and can be detected in cerebrospinal fluid and plasma. Emerging…

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