Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses
Figure 3
Secretion of AP from APP and its oligomerization. AP is secreted by the cleavage of the APP N-terminus by -secretase (BACE), followed by the intramembrane cleavage of the C-terminus by -secretase. APP also binds to Cu or Zn. Human AP and rodent AP differ by 3 amino acids (Arg5, Tyr10, and His13). AP monomers form random-coil structures. However, under aging conditions or the existence of trace metals such as Al, Zn, and Cu, AP self-aggregates and oligomerizes (dimmer to protofibrils), and then forms insoluble amyloid fibrils. Although monomeric APs are not toxic, oligomeric APs induce marked neuronal death.