Fig. 1: Overview of the processing and metabolism of APP.
From: Amyloid-β and Tau in Alzheimer’s disease: pathogenesis, mechanisms, and interplay
In neurons, the sequential cleavage of full-length APP by first β-secretase and then γ-secretase generates Aβ peptide as well as sAPPβ and AICD components. The accumulative production of Aβ leads to its aggregation and subsequent oligomerization. The oligomerized Aβs then further aggregate, leading to the formation of extracellular Aβ plaques. These plaques drive the pathogenesis of AD and its phenotypes. Alternatively, in the non-amyloidogenic pathway, the cleavage of APP by α-secretase occurs at a site that pertains to the Aβ domain, thereby not yielding an Aβ peptide and instead releasing the sAPP component and leaving the C83 domain embedded in the membrane. Intracellularly, AICD may be further cleaved by caspases, which produce Jcasp and C31 fragments.
