Figure 2.

Schematic representation of nonamyloidogenic and amyloidogenic processing of the amyloid precursor protein (APP): nonamyloidogenic processing of APP is mediated by α-secretase followed by γ-secretase, releasing soluble APPα and intracellular fragments AICD and P3. Amyloidogenic processing involves cleavage by β-secretase followed by γ-secretase, which releases toxic Aβ₁₋₄₂ [79,80]. Aβ can oligomerize and form cytotoxic metal-Aβ complexes that generate ROS, disrupt the lipid bilayer, compromise mitochondrial function, or initiate aberrant signaling cascades. Activation of p38 by ROS phosphorylates tau results in NFTs. IC: intracellular, EC: extracellular, NFTs: neurofibrillary tangles, and PM: plasma membrane.