The decades of evidence that showcase the role of amyloid precursor protein (APP), and its fragment amyloidβ (Aβ), in Alzheimer's disease (AD) pathogenesis are irrefutable. However, the absolute focus on the single APP metabolite Aβ as the cause for AD has resulted in APP and its other fragments that possess toxic propensity, to be overlooked as targets for treatment. The complexity of its processing and its association with systematic metabolism suggests that, if misregulated, APP has the potential to provoke an array of metabolic dysfunctions. This review discusses APP and several of its cleaved products with a particular focus on their toxicity and ability to disrupt healthy cellular function, in relation to AD development. We subsequently argue that the reduction of APP, which would result in a concurrent decrease in Aβ as well as all other toxic APP metabolites, would alleviate the toxic environment associated with AD and slow disease progression. A discussion of those drug-like compounds already identified to possess this capacity is also included.
Keywords: Alzheimer’s disease; Amyloid precursor protein; C-terminal fragment β (CTFβ); C31 peptide; Posiphen.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.