Lack of evidence to support the association of polymorphisms within the alpha- and beta-secretase genes (ADAM10/BACE1)

Cleavage of the amyloid precursor protein (APP) occurs through either an amyloidogenic or a non-amyloidogenic pathway. The first results in the generation of beta-amyloid (A beta) and is initiated through cleavage by the beta-site amyloid beta A4 precursor protein-cleaving enzyme 1 (BACE1). The second precludes the formation of A beta through cleavage by alpha-secretase, an enzyme's activity demonstrated in a disintegrin metalloproteinase, ADAM10. To assess the contribution of variants in the BACE1 and ADAM1 0 genes we used a detailed fine mapping approach. Genotyping of 11 single nucleotide polymorphisms covering the complete BACE1 gene, and 27 covering the entire ADAM10 gene, revealed no single-marker or haplotypic association with AD. We conclude that, in this present study, neither ADAM1 0 nor BACE1 present with any evidence to suggest that they are major candidate genes involved in conferring risk for AD. (C) 2009 Elsevier Inc. All rights reserved.