GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES

The apolipoprotein E type 4 allele (APOE-epsilon4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon4 alleles in 42 families with late onset AD. Thus APOE-epsilon4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon4 was virtually sufficient to cause AD by age 80.