title: Mutations in the open reading frame of the beta-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease.
abstract: Amyloid beta-peptide (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD). The gene encoding the beta-site APP cleaving enzyme (BACE), one of two enzymes that sequentially cleave the beta-amyloid precursor protein to generate Abeta, has recently been cloned. We tested the hypothesis that BACE might be genetically associated with AD by linkage analysis (56 pedigrees), by direct nucleotide sequencing of the entire open reading frame (20 subjects with familial AD, and 10 subjects with sporadic AD) and by allelic association analysis (155 AD cases and 173 non-demented controls). Our results revealed no evidence for either genetic linkage or allelic association between BACE and AD, and no coding sequence mutations were detected in the open reading frame of the BACE gene. These data suggest that while BACE protein plays an important role in the pathogenesis of AD, and may be a robust therapeutic target, it is unlikely to be a major AD susceptibility locus.
authors.affiliation: Department of Medicine, Boston University School of Medicine, MA 02118, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nicolaou
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Song
authors.forename: C A
authors.initials: CA
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Orlacchio
authors.forename: T
authors.initials: T
authors.lastname: Kawarai
authors.forename: H
authors.initials: H
authors.lastname: Medeiros
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: S
authors.initials: S
authors.lastname: Sorbi
authors.forename: E
authors.initials: E
authors.lastname: Richard
authors.forename: E I
authors.initials: EI
authors.lastname: Rogaev
authors.forename: Y
authors.initials: Y
authors.lastname: Moliaka
authors.forename: A C
authors.initials: AC
authors.lastname: Bruni
authors.forename: R
authors.initials: R
authors.lastname: Jorge
authors.forename: M
authors.initials: M
authors.lastname: Percy
authors.forename: R
authors.initials: R
authors.lastname: Duara
authors.forename: L A
authors.initials: LA
authors.lastname: Farrer
authors.forename: P
authors.initials: P
authors.lastname: St Georg-Hyslop
authors.forename: E A
authors.initials: EA
authors.lastname: Rogaeva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D004252:DNA Mutational Analysis; D010450:Endopeptidases; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human