TREM2 as a possible link between Alzheimer's disease and diabetes mellitus.

Alzheimer's disease (AD) and diabetes mellitus (DM) represent escalating global health burdens, with epidemiological and clinical studies demonstrating a strong association between them. Diabetic patients face a significantly increased risk of AD, and poor glycemic control can accelerate AD progression. Chronic low-grade inflammation is increasingly recognized as a central mechanism bridging the two diseases. Triggering receptor expressed on myeloid cells 2 (TREM2), a key immune regulator, has emerged as a critical player in both AD and DM. In AD, TREM2 is specifically expressed on microglia, mediating neuroinflammatory and neurodegenerative processes while regulating both amyloid-β (Aβ) and Tau pathology. In DM, TREM2 contributes to insulin resistance and metabolic dysregulation. Genetic variants of TREM2 are established risk factors for AD, while altered TREM2 expression correlates with DM pathology. This review summarizes TREM2's structural and functional characteristics, its dual roles in AD and DM, and its potential as a therapeutic target. Elucidating these shared TREM2-mediated mechanisms may provide novel insights into the pathological interplay between AD and DM and inform precision therapeutic strategies.