TREM2 and microglial immunity in Alzheimer's disease: mechanisms, genetics, and therapeutic opportunities.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing molecular, genetic, and preclinical mechanistic literature.
PubMed 41789102 · doi:10.3389/fimmu.2026.1739875
What was done
This narrative review synthesized recent genetic, molecular, and preclinical literature evaluating triggering receptor expressed on myeloid cells 2 (TREM2) in Alzheimer's disease pathogenesis. It examined TREM2-mediated regulation of microglial phagocytosis, metabolism, and survival, the TREM2-APOE pathway in disease-associated microglia, the impact of the R47H mutation, and the therapeutic potential of soluble TREM2 and targeted immunotherapies.
What was found
The abstract reports qualitative mechanistic summaries rather than quantitative primary data or effect estimates. It reports that TREM2 regulates microglial response to amyloid-beta and neuronal injury, that loss-of-function variants like R47H exacerbate amyloid pathology and neuroinflammation, and that TREM2-targeted immunotherapies improve plaque encapsulation and cognitive outcomes in preclinical models.
Why it matters
The review outlines how microglial innate immune pathways intersect with core Alzheimer's pathologies (amyloidosis and tauopathy), summarizing the rationale for TREM2-directed diagnostics and disease-modifying immunotherapies.
Limits
As a narrative review, it presents no original empirical data, quantitative meta-analyses, or systematic study selection criteria. Therapeutic and cognitive findings highlighted are derived from preclinical animal models, and clinical efficacy or safety in human Alzheimer's disease patients cannot be established from this summary.
Cited by
- supports Microglial phagocytosis of proteins is impaired in individuals with Alzheimer's disease.