title: Dose-dependent association of apolipoprotein E allele epsilon 4 with late-onset, sporadic Alzheimer's disease.
abstract: We examined the apolipoprotein E (apo E) genotypes in 47 patients with late-onset sporadic Alzheimer's disease (mean age at onset +/- standard deviation, 72.2 +/- 6.4 years), 8 with late-onset familial Alzheimer's disease (75.5 +/- 5.1 years), 18 with early-onset sporadic Alzheimer's disease (52.8 +/- 4.7 years), and 10 with early-onset familial Alzheimer's disease (52.0 +/- 6.8 years) in Japan and compared them with genotypes in control subjects. In late-onset sporadic Alzheimer's disease, apo E-epsilon 4 frequency increased significantly (epsilon 4 frequency: 0.34 vs 0.095 in controls, p < 0.0001), and the odds ratio, which represents the strength of association between Alzheimer's disease and apo E-epsilon 4, markedly increased with increasing dose of apo E-epsilon 4 gene (3 [95% confidence interval, 2-6] in one dose; 43 [95% confidence interval, 12-154] in two doses). This study also suggested that apo E-epsilon 4 is associated with both late-onset (epsilon 4: 0.31) and early-onset familial Alzheimer's disease (epsilon 4: 0.35). In contrast, we found no association between apo E-epsilon 4 and early-onset sporadic Alzheimer's disease (epsilon 4: 0.08). These results indicate that the risk of developing late-onset sporadic Alzheimer's disease is markedly dependent on the dose of apo E-epsilon 4, while apo E-epsilon 4 does not appear to be a major risk factor for early-onset sporadic Alzheimer's disease.
authors.affiliation: Department of Neurology, University of Tsukuba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa-Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Komatsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Arinami
authors.forename: E
authors.initials: E
authors.lastname: Oguni
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
authors.forename: S
authors.initials: S
authors.lastname: Shoji
authors.forename: H
authors.initials: H
authors.lastname: Hamaguchi
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E