The amyloid precursor protein (APP) is considered to play a central role in the pathogenesis of Alzheimer’s disease (AD). APP is the precursor of amyloid β-protein (Aβ), the main component of amyloid plaques, and as such has given rise to the amyloid cascade hypothesis for AD, which posits that the misprocessing and abnormal regulation of APP leads to the gradual overproduction or accumulation of Aβ into oligomers and extracellular plaques, initiating a sequence of events that results in AD (Hardy and Selkoe, 2002). APP is a type I transmembrane protein with a large N-terminal extracellular domain and a short cytoplasmic domain. APP undergoes multiple proteolytic steps: cleavage by either α- or β-secretase releases the large APP ectodomain, sAPPα and sAPPβ respectively; leaving the membrane-anchored C-terminal fragments (CTFs) (Sisodia et al., 1993; Turner et al., 2003). The CTFs can be further cleaved by γ-secretase to generate Aβ peptides, while releasing the APP intracellular domain (AICD), which is thought to contribute to cell signaling or cell death (Konietzko, 2011).
