Prospective study of risk factors for Alzheimer's disease: Results at 7.5 years

Objective: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon 4 genotype. Method: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. Results: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE epsilon 4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the epsilon 4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. Conclusions: These results indicate that increased platelet membrane fluidity is not produced by the APOE epsilon 4 allele. Instead, increased platelet membrane fluidity and the epsilon 4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different.