AD follows a relatively stereotyped pro-gression with onset at 47.6±3.0 years and death at 58.8±4.0 years. During prospective follow-up studies of this kin-dred, we identified a person who carries the APP717 mutation yet who, at the age of 1 standard deviation (SD) above the mean age of onset in this pedigree, showed no sign of clinical disease on neurologic or neuropsychologic tests or on computerized axial tomography or magnetic resonance imaging scans. Furthermore, this person has continued to remain asymptomatic at 2 SDs beyondthe mean ageof onset in this pedigree. Other, younger relatives of this person who also carry the APP717 muta-tion, however, are clinically affected. E. H. Corder et al.(2) recently ob-served that inheritance of the e4 alleleof the apolipoprotein E (APOE) gene appeared to influence the risk (or the age of onset, or both) of late onset AD in a" dose dependent" fashion. This finding prompt-ed us to investigate the APOE genotypes of the person under study and of other clinically affected relatives. All (n= 3) living clinically affected family members with the APP717 mutation had E3/E4 genotypes at the APOE gene, while the older, asymptomatic carrier of the APP717 mutation lacked the E4 allele at APOE (genotype E2/E3). Schmechel et al.(3) found a relationship between the pres-ence of the E4 allele and the density of plaques containing APP in tissue from people affected by AD who also carry wild-type APP genes.