The apolipoprotein epsilon 4 allele in patients with Alzheimer's disease.
Apolipoprotein E (APO-E) binds to the beta-amyloid peptide and is present in senile neuritic plaques in Alzheimer's disease (AD). The epsilon 4 isoform of APO-E has been associated with both sporadic and familial late-onset AD, implying a causal role. Among patients and control subjects similar in age, gender, and ethnic group from the New York City community of Washington Heights-Inwood, we found that the odds ratio (OR) for AD associated with homozygosity for APO-epsilon 4 was 17.9 (95% confidence interval [CI], 4.6-69.8) and that associated with heterozygosity for APO-epsilon 4 was 4.2 (95% CI, 1.8-9.5) compared with persons with other APO-E genotypes. The association was stronger among patients with sporadic disease (OR = 10.3; 95% CI, 3.4-31.1) than among those with a family history of dementia in a first-degree relative (OR = 0.9; 95% CI, 0.1-13.5). The association between APO-epsilon 4 and AD did not differ according to age at onset (< 65 vs > or = 65), but appeared to vary across the 3 ethnic groups investigated (black, Hispanic, and white). Our data confirm the association between AD and APO-epsilon 4 and support the hypothesis that the APO-epsilon 4 allele either confers genetic susceptibility to AD or may be in linkage disequilibrium with another susceptibility locus. Ethnic variability in the allelic frequency of APO-epsilon 4 in the elderly warrants further investigation.
Mayeux
R
R
G.H. Sergievsky Center, Columbia University, New York, NY 10032.
Stern
Y
Y
Ottman
R
R
Tatemichi
T K
TK
Tang
M X
MX
Maestre
G
G
Ngai
C
C
Tycko
B
B
Ginsberg
H
H
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D044383:Black People; D016001:Confidence Intervals; D005190:Family; D005260:Female; D005784:Gene Amplification; D008040:Genetic Linkage; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012016:Reference Values; D044465:White People
D001057:Apolipoproteins E