Fig. (1).

Singling pathways involved in the progression of AD. APP is successively cleaved by the β-secretase and γ-secretase to produce the Aβ, meanwhile, the metal ions (Fe, Cu, and Zn) could enhance the activity of β-secretase. With the help of metal ions, the Aβ is deposited to form senile plaques. On the other hand, the Aβ could induce microglial activation and astrocytic activation to produce inflammatory factors. Increased contents of metal ions lead to CDK5 and GSK3α/β activation, thus promoting tau hyperphosphorylation and NFTs formation. Iron overload is also observed in the cerebral neurons, which results in ferroptosis. All the aforementioned pathways participate in the progression of AD.