MAPT and infection: Not fully understood; Key mechanisms include beta-amyloid and tau misfolding and aggregation, mitochondrial dysfunction, oxidative stress, impairment of protein clearance, and neuroinflammation. Infections with pathogens (e.g., HSV-1 or oral porphyromonas gingivalis or gut microbiota) and exposures to metal ions can trigger beta-amyloid aggregation (3, 88, 89), which further induces tau aggregation (90) and neuroinflammation, leading to neuronal degeneration and loss in the hippocampus and associated regions (91)