Fig. 1

An overview of pathogenesis of AD. (1) In the amyloid-producing pathway, Aβ is produced by the abnormal cleavage of APP by β-secretase 1 (BACE1) and γ-secretase. First, BACE1 cleaved the APP to produce sAPP and C-99 fragments. The C-99 fragment was cleaved by γ-secretase to produce two AICD fragments and an insoluble Aβ fragment. (2) Under normal circumstances, tau can bind to tubulin and stabilize microtubules, playing an important role in maintaining cell polarization, axonal transport and promoting neuronal growth. When tau is over-phosphorylated, tau dissociates from microtubules and aggregates into helical filaments (PHFS), which further aggregates to form NFTs, destabilizing microtubules and ultimately leading to neurofibrillary degeneration. (3) ACh is synthesized by acetyl-CoA and choline and catalyzed by choline acetyltransferase. Acetylcholinesterase in the synaptic cleft terminates signaling by hydrolyzing ACh. (4) Aβ stimulates the activation of microglia and astrocytes and induces reactive gliosis and proinflammatory signaling cascades. Activated microglia and astrocytes reduced Aβ clearance. (5) ROS promote the course of AD mainly through macromolecular peroxidation, Aβ metal ion REDOX potential and mitochondrial dysfunction, and affect cellular homeostasis, free radical production and increase the production of Aβ and p-tau