Figure 1
From: Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease
Schematic diagram outlining mechanisms of oligomeric Aβ-induced synaptic dysfunction. At pathological concentrations, Aβ oligomers may interact with multiple astrocytic, microglial, and neuronal synaptic proteins, including α7-AChRs and NMDARs, triggering a series of toxic synaptic events. These events include aberrant activation of NMDARs (especially NR2B-containing extrasynaptic NMDARs), elevated neuronal calcium influx, calcium-dependent activation of calcineurin/PP2B and its downstream signal transduction pathways, involving cofilin, GSK-3β, CREB, and MEF2. This results in aberrant redox reactions and severing/depolymerizing F-actin, tau-hyperphosphorylation, endocytosis of AMPARs, and eventually leads to synaptic dysfunction and cognitive impairment.