Figure 3.

Secretion of AβP from APP and its oligomerization. AβP is secreted by the cleavage of the APP N-terminus by β-secretase (BACE), followed by the intramembrane cleavage of the C-terminus by γ-secretase. APP also binds to Cu or Zn. Human AβP and rodent AβP differ by 3 amino acids (Arg⁵, Tyr¹⁰, and His¹³). AβP monomers form random-coil structures. However, under aging conditions or the existence of trace metals such as Al, Zn, and Cu, AβP self-aggregates and oligomerizes (dimmer to protofibrils), and then forms insoluble amyloid fibrils. Although monomeric AβPs are not toxic, oligomeric AβPs induce marked neuronal death.