Fig. 1
From: The role of pathological tau in synaptic dysfunction in Alzheimer’s diseases
Pathological tau induces synaptic dysfunction. At presynaptic terminals, the interaction of pathological tau with synaptogyrin-3 on synaptic vesicles hampers vesicle mobility and impairs presynaptic vesicle cycling. Pathological tau impairs neuronal endocytosis through the miR-132–meCP2–dynamin 1 pathway. Pathological tau induces tagging of synapses by complement initiation factor (C1q) and activates synapse phagocytosis by microglia. The infiltration of pathological tau into postsynapses recruits Fyn to NMDAR/PSD-95 complexes and causes excitotoxicity mediated by amyloid-β and excessive glutamate. Accumulation of acetylated tau contributes to KIBRA deficiency, which blocks the activity-dependent F-actin polymerization and disrupts AMPA receptor membrane anchoring at postsynapses