title: Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals.
abstract: Recent genetic studies show that the apolipoprotein E epsilon 4 allele (ApoE-epsilon 4) is a risk factor for Alzheimer's disease (AD). If ApoE-epsilon 4 individuals develop AD as they get older, we would expect a decrease in ApoE-epsilon 4 allele frequency with increasing age. We found a marked decline in ApoE-epsilon 4 allele frequency with advancing age in both AD and cognitively normal controls (p < 0.003), although in all age groups the ApoE-epsilon 4 allele was overrepresented (p < 0.0001). Nonetheless, a few cognitively normal nonagenarians were ApoE-epsilon 4 positive. Thus, our data support two new conclusions: (1) the ApoE-epsilon 4 associated risk for AD is age-dependent, probably due to censoring by the earlier development of AD in ApoE-epsilon 4 individuals, and (2) despite the ApoE-epsilon 4 associated risk for AD, it is possible to reach extreme old age with normal cognition.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston 02114.
authors.forename: G W
authors.initials: GW
authors.lastname: Rebeck
authors.forename: T T
authors.initials: TT
authors.lastname: Perls
authors.forename: H L
authors.initials: HL
authors.lastname: West
authors.forename: P
authors.initials: P
authors.lastname: Sodhi
authors.forename: L A
authors.initials: LA
authors.lastname: Lipsitz
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012044:Regression Analysis
chemical_list: D001057:Apolipoproteins E