
Amyloid precursor protein (APP) is a type I integral membrane protein ubiquitously expressed in many tissues and concentrated in the synapses of neurons. It has three predominant splice variants: APP695, APP751, and APP770. The majority of APP is cleaved at the plasma membrane by the α-secretase in the non-amyloidogenic pathway. The amyloidogenic pathway starts with β-secretase cleavage by BACE1 on the N-terminal part of the Aβ domain, releasing sAPPβ from a membrane-anchored fragment named βCTF or C99, which is subsequently cleaved by γ-secretase to release Aβ.
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