A Narrative Review of TREM2 Signaling in Perioperative Neurocognitive Disorders: Mechanisms, Biomarkers, and Therapeutic Targets

Background: Perioperative neurocognitive disorders (PNDs) represent one of the most prevalent and damaging complications following major surgery in elderly patients. Within the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is almost exclusively localized to the microglia and serves as a key integrator in maintaining neuroinflammatory homeostasis. This review aims to summarize the signaling mechanisms and roles of TREM2 in PNDs, providing guidance for future research and clinical translation. Materials and Methods: This narrative review searched PubMed, Web of Science, and Scopus for relevant evidence on TREM2 in perioperative neurocognitive disorders, supplemented by reference-list screening. Results: TREM2 mediates neuroprotection in surgery-induced PNDs through anti-inflammatory effects, regulation of mitophagy and oxidative stress, and maintenance of synaptic integrity. Anesthesia, pain, aging, and comorbidities modulate TREM2 signaling in the perioperative brain. Soluble TREM2 (sTREM2) shows potential as a biomarker for PNDs. Recent advances in TREM2-targeted interventions lay the mechanistic groundwork for future studies. Conclusions: TREM2 is a promising neuroprotective target in PNDs, though its context-dependent effects warrant further study to enable precise perioperative translation.