title: Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease.
abstract: 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.
authors.affiliation: Division of Neurology, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: E H
authors.initials: EH
authors.lastname: Corder
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: N J
authors.initials: NJ
authors.lastname: Risch
authors.forename: W J
authors.initials: WJ
authors.lastname: Strittmatter
authors.forename: D E
authors.initials: DE
authors.lastname: Schmechel
authors.forename: P C
authors.initials: PC
authors.lastname: Gaskell
authors.forename: J B
authors.initials: JB
authors.lastname: Rimmler
authors.forename: P A
authors.initials: PA
authors.lastname: Locke
authors.forename: P M
authors.initials: PM
authors.lastname: Conneally
authors.forename: K E
authors.initials: KE
authors.lastname: Schmader
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E