title: Apolipoprotein E4 allele and Alzheimer disease: examination of allelic association and effect on age at onset in both early- and late-onset cases.
abstract: An increased frequency of the apolipoprotein E type 4 allele (APOE-4) has previously been associated with both late-onset sporadic and late-onset familial Alzheimer disease (AD) [Strittmatter et al. (1993) Proc Natl Acad Sci USA 90:1977-1981; Saunders et al. (1993a) Neurology 43:1467-1472]. To further investigate this association we genotyped affected individuals from 92 separate AD pedigrees including both early- and late-onset cases. An increased frequency of the APOE-4 allele was found only among the late-onset cases, both familial and sporadic, confirming the earlier reports. In addition, age at onset was significantly decreased in the APOE-4 homozygotes (in late onset families) compared to either APOE-4 heterozygotes or individuals not carrying an APOE-4 allele. We also observed a significantly decreased frequency of the APOE-2 allele in both the early- and late-onset familial cases. These results strengthen the argument for a direct role of APOE in susceptibility to AD.
authors.affiliation: Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Locke
authors.forename: P M
authors.initials: PM
authors.lastname: Conneally
authors.forename: R E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D010375:Pedigree
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E