Amyloid-beta precursor protein (APP) (APP)

Amyloid-beta precursor protein (APP) is a type I transmembrane protein that plays a critical role in the central nervous system, where it is involved in synapse formation, neural plasticity, and iron homeostasis [UniProt: P05067]. The "Beta-amyloid pathway" refers to the sequential proteolytic processing of APP by beta-secretase (BACE1) and gamma-secretase, leading to the production of amyloid-beta (Aβ) peptides [PubMed: 30633919]. In Alzheimer's disease, these peptides aggregate into neurotoxic oligomers and insoluble extracellular plaques, which are thought to trigger a cascade of neurodegeneration [NIH: Alzheimer's Disease Fact Sheet]. Therapeutic interventions targeting this pathway include monoclonal antibodies that facilitate the clearance of Aβ plaques and small-molecule inhibitors designed to block the enzymes responsible for Aβ production [FDA: Leqembi Prescribing Information]. While recent anti-amyloid antibodies like lecanemab and donanemab have demonstrated clinical efficacy in slowing cognitive decline, the pathway presents significant challenges, including the risk of amyloid-related imaging abnormalities (ARIA) and the historical failure of secretase inhibitors due to off-target effects and lack of efficacy [PubMed: 37402880].

Other names

APPAmyloid-beta A4 proteinABPPAPPICerebral vascular amyloid peptidePreA4Beta-amyloid pathway

Inhibition of amyloid-beta production via BACE or gamma-secretase inhibition, and clearance of amyloid-beta aggregates via monoclonal antibodies.