Amyloid β 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) cleaves the beta -amyloid (AB) precursor protein at the N-terminal end of A beta, allowing for the production of A beta by C-terminal gamma -secretase cleavage. We hypothesized that over-activity of BACE might lead to the overproduction of A beta, hence causing Alzheimer's disease (AD). Molecular genetic analyses of BACE in 9 autosomal dominant AD families and a population-based sample of 101 presenile AD cases did not identify genetic linkage, pathogenic mutations or genetic association with BACE, suggesting that BACE is not genetically involved in the etiology of AD. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.