title: Specific BACE1 genotypes provide additional risk for late-onset Alzheimer disease in APOE epsilon 4 carriers.
abstract: Alzheimer disease (AD) is characterized neuropathologically by neurofibrillary tangles and senile plaques. A key component of plaques is A beta, a polypeptide derived from A beta-precursor protein (APP) through proteolytic cleavage catalyzed by beta and gamma-secretase. We hypothesized that sequence variation in genes BACE1 (on chromosome 11q23.3) and BACE2 (on chromosome 21q22.3), which encode two closely related proteases that seem to act as the APP beta-secretase, may represent a genetic risk factor for AD. We analyzed the frequencies of single nucleotide polymorphisms (SNPs) in BACE1 and BACE2 genes in a community-based sample of 96 individuals with late-onset AD and 170 controls selected randomly among residents of the same community. The genotype data in both study groups did not demonstrate any association between AD and BACE1 or BACE2. After stratification for APOE status, however, an association between a BACE1 polymorphism located within codon V262 and AD in APOE epsilon 4 carriers was observed (P = 0.03). We conclude that sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; however, a combination of a specific BACE1 allele and APOE epsilon 4 may increase the risk for Alzheimer disease over and above that attributed to APOE epsilon 4 alone.
authors.affiliation: Department of Geriatrics, Belle-Idée Hospital Center, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gold
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
authors.forename: François R
authors.initials: FR
authors.lastname: Herrmann
authors.forename: Agnès
authors.initials: A
authors.lastname: Michon
authors.forename: Reinhild
authors.initials: R
authors.lastname: Mulligan
authors.forename: Geneviève
authors.initials: G
authors.lastname: Duriaux Saïl
authors.forename: Constantin
authors.initials: C
authors.lastname: Bouras
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Giannakopoulos
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D016022:Case-Control Studies; D010450:Endopeptidases; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human