Proteolytic Processing of the Alzheimer's Disease Amyloid Precursor Protein in Brain and Platelets

Abstract

Proteolytic processing of the amyloid precursor protein by β -and γ-secretases results in the production of Alzheimer's disease (AD) Aβ amyloid peptides. Modulation of secretase activity is being investigated as a potential therapeutic approach. Recent studies with human brain have revealed that the β-secretase protein, BACE, is increased in cortex of AD patients. Analysis of βCTF (or C99), the amyloid precursor protein (APP) product of BACE cleavage that is the direct precursor to Aβ, shows it is also elevated in AD, underlying the importance of β-secretase cleavage in AD pathogenesis. The C-terminal product of γ-secretase cleavage of APP, ECTF (or AICD), is enriched in human brain cortical..