APOLIPOPROTEIN-E4 ALLELE AND ALZHEIMERS-DISEASE - EXAMINATION OF ALLELIC ASSOCIATION AND EFFECT ON AGE AT ONSET IN BOTH EARLY-ONSET AND LATE-ONSET CASES

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 affec ted individuals from 92 separate AD pedigrees including both early- an d late-onset cases. An increased frequency of the APOE-4 allele was fo und only among the late-onset cases, both familial and sporadic, confi rming 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 AP OE-2 allele in both the early- and late-onset familial cases. These re sults strengthen the argument for a direct role of APOE in susceptibil ity to AD. (C) 1995 Wiley-Liss, Inc.