Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses

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.