TREM2 Cancer Research Results

TREM2 - Triggering Receptor Expressed on Myeloid Cells 2

Type: Transmembrane immune receptor / microglial receptor / innate immune signaling protein

Function: TREM2 is expressed predominantly on microglia in the central nervous system and regulates phagocytosis, lipid sensing, cellular metabolism, survival, proliferation, inflammatory signaling, and microglial responses to neuronal injury and protein aggregates. TREM2 signals primarily through adaptor proteins such as TYROBP/DAP12 and activates pathways including SYK, PI3K-AKT-mTOR, and PLCγ2.

Alzheimer's Disease: ↓ / impaired TREM2 signaling is generally unfavorable. Loss-of-function TREM2 variants increase the risk of late-onset Alzheimer's disease and can impair microglial phagocytosis, metabolic fitness, amyloid plaque containment, and responses to neuronal injury. Functional TREM2 signaling can promote microglial clustering around Aβ plaques, plaque compaction, debris clearance, and microglial survival.

Favorable Direction in Alzheimer's Disease: ↑ Functional TREM2 signaling is generally favorable, particularly when restoring deficient microglial responses. However, TREM2 effects are disease-stage and context dependent, so excessive or prolonged activation should not automatically be considered beneficial.

Genetic Relevance: Rare TREM2 variants, particularly R47H, are established genetic risk factors for late-onset Alzheimer's disease and are associated with reduced or altered receptor function.

Related Biomarker: Soluble TREM2 (sTREM2) is generated by proteolytic shedding or alternative splicing and can be measured in cerebrospinal fluid and plasma. sTREM2 should be considered separately from membrane-bound TREM2 when interpreting biomarker studies.