The Dual Role of TREM2 in 5xFAD Alzheimer's Disease Mouse Models :Implications for Targeting Strategies

This review explores the dual role of TREM2 (Triggered Receptor Expressed on Myeloid cells 2) in the 5xFAD Alzheimer's disease (AD) mouse model and its potential implications for targeted therapeutic strategies. TREM2, a key regulator of microglia, exhibits complex dual effects of neuroprotection and neurotoxicity in AD pathogenesis. In recent years, with deepening insights into AD pathogenesis, TREM2's roles in Aβ clearance, metabolic homeostasis maintenance, and inflammatory regulation have garnered increasing attention. However, TREM2 may exhibit diametrically opposed functions across different disease stages and activation states, posing challenges for targeted therapies. This paper systematically elucidates TREM2's protective role in the 5xFAD model (e.g., promoting Aβ clearance, maintaining neuronal function) alongside its potential harmful effects (e.g., driving pathological inflammation), and analyzes the mechanisms underlying its dual roles (e.g., disease stage dependency, activation level dependency). Based on existing research, this paper further summarizes the challenges facing TREM2-targeted therapies and explores novel strategies for precisely regulating TREM2 function, providing theoretical foundations and directions for future AD treatments.