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. Author manuscript; available in PMC: 2019 Sep 25.
Published in final edited form as: JAMA Neurol. 2016 Jul 1;73(7):867–874. doi: 10.1001/jamaneurol.2016.0301

Figure 1. Proteolytic Processing of Amyloid Precursor Protein (APP) by β- and γ-Secretases to Generate Amyloid β (Aβ) Protein.

Figure 1.

When APP undergoes nonamyloidogenic proteolytic cleavage by α- and γ-secretases, p3 instead of Aβ is generated. A small number of APP molecules is proteolytically processed by β-secretase and generates an N-terminal soluble APP and a 12-kDa C-terminal stub of APP, which is cleaved by γ-secretase to yield Aβ and amyloid intracellular domain. The PS1 and PS2 genes carry the active site of γ-secretase complex. Proteins encoded by multiple risk genes associated with late-onset Alzheimer disease are involved in Aβ clearance. The SORL1, PICALM, and CD2AP genes regulate APP endocytosis (vs retromer-mediated APP recycling) and Aβ generation in endosome-lysosomes.