Beta-amyloid (Ab) deposition in the brain is the hallmark of Alzheimer's Disease (AD). To initiate Ab formation, beta-secretase cleaves APP at the N-terminus of Ab to release APPsb (~100kD soluble NT-fragment), and C99, a 12-kD CT membrane fragment. Alternatively, alpha-secretase cleaves within the Ab to prevent the formation of Ab. Cleavage by a-secretase produces a soluble N-terminal fragment, APPsa, and a 10-kD membrane C-terminal fragment, C83. Both C99 and C83 can be further cleaved by gamma-secretase releasing Ab and a nonpathogenic p3 peptide, respectively.
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