Amyloid beta secretase gene (BACE) is neither mutated in nor associated with early-onset Alzheimer's disease

The beta-site of beta -amyloid precursor protein cleaving enzyme (BACE) cle aves the beta -amyloid (AB) precursor protein at the N-terminal end of A be ta, allowing for the production of A beta by C-terminal gamma -secretase cl eavage. We hypothesized that over-activity of BACE might lead to the overpr oduction of A beta, hence causing Alzheimer's disease (AD). Molecular genet ic analyses of BACE in 9 autosomal dominant AD families and a population-ba sed sample of 101 presenile AD cases did not identify genetic linkage, path ogenic mutations or genetic association with BACE, suggesting that BACE is not genetically involved in the etiology of AD. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.