Figure 2.

Reciprocal toxicity between Aβ and tau. Aβ precursor protein (APP) is cleaved by β/γ secretases to form Aβ. Aβ activates GSK-3β and CDK-5 to phosphorylate tau protein and activate caspase-3 and calpain 1 to hydrolyse tau protein and form tau oligomers. Phosphorylated tau protein interacts with Fyn. Aβ-activated Fyn also accelerates tau phosphorylation and binds to tau. Phosphorylated Fyn acts on NR2B to form the NMDAR-PSD95-Fyn complex. NMDARs are activated to increase Ca²⁺, which affects the function of mitochondria. Aβ and phosphorylated tau induce the fusion and fission of mitochondria by acting on Drp1, which induces the dysfunction of mitochondrial dynamics and ultimately leads to reactive oxygen species (ROS) overproduction and apoptosis.