Smog, sugar, and synapses: Unraveling the PM2.5-insulin resistance-Alzheimer’s disease axis

Chronic exposure to fine particulate matter (PM2.5) and insulin resistance (IR) are each linked to Alzheimer's disease (AD), but IR has not been systematically positioned as a mechanistic conduit through which PM2.5 heightens AD vulnerability. Drawing on epidemiological, animal, and cellular studies, this review outlines converging pathways along a PM2.5-IR-AD axis: chronic neuroinflammation, oxidative stress and mitochondrial dysfunction, blood-brain barrier disruption, and impaired amyloid-β (Aβ) clearance. Across sections, study-specific limitations are comprehensively discussed. Positioning IR as a central node linking PM2.5 exposure to AD reframes air pollution as a modifiable metabolic-neurologic risk. Potential therapeutic and preventive avenues are also highlighted. Future work could prioritize longitudinal and interventional studies that directly interrogate the PM2.5-IR-AD triad and refine biomarkers to guide precision prevention.