Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease.
Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the epsilon 2 allele, in addition to the dose effect of the epsilon 4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of epsilon 4 alleles, risk of AD is lowest in subjects with the epsilon 2/epsilon 3 genotype, with an additional 23% of AD attributable to the absence of an epsilon 2 allele. The opposite actions of the epsilon 2 and epsilon 4 alleles further support the direct involvement of APOE in the pathogenesis of AD.
Corder
E H
EH
Division of Neurology, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina 27710.
Saunders
A M
AM
Risch
N J
NJ
Strittmatter
W J
WJ
Schmechel
D E
DE
Gaskell
P C
PC
Rimmler
J B
JB
Locke
P A
PA
Conneally
P M
PM
Schmader
K E
KE
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors
D001057:Apolipoproteins E