The amyloid precursor protein: a converging point in Alzheimer's disease

The decades of evidence that showcase the role of amyloid precursor protein (APP), and its fragment amyloid beta (A beta), in Alzheimer's disease (AD) pathogenesis are irrefutable. However, the absolute focus on the single APP metabolite A beta 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 A beta 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.

Automated summary

Decades of evidence have shown the important role of amyloid precursor protein (APP) and its fragment amyloid beta (A beta) in the pathogenesis of Alzheimer's disease (AD). However, the excessive focus on A beta as the cause of AD has led to the neglect of other toxic fragments of APP as potential treatment targets. Reduction of APP and its toxic metabolites could alleviate the toxic environment associated with AD and slow disease progression.