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 platele t membrane fluidity as a putative risk factor for Alzheimer's disease and i ts relationship to the APOE epsilon 4 genotype. Method: This report describ es the results of a prospective, longitudinal study of 330 initially asympt omatic, first-degree relatives of probands with Alzheimer's disease. Result s: Nine incident cases of Alzheimer's disease were detected during the firs t 2,220 subject-years of the follow-up period. Age, increased platelet memb rane fluidity, and the APOE epsilon 4 allele made significant independent c ontributions to the risk of developing Alzheimer's disease, while sex and y ears of education did not. Increased platelet membrane fluidity was associa ted 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 indica te that increased platelet membrane fluidity is not produced by the APOE ep silon 4 allele. Instead, increased platelet membrane fluidity and the epsil on 4 allele appear to make significant independent contributions to the ris k of developing Alzheimer's disease among the first-degree relatives of pat ients with this disorder. Moreover, the age ranges over which these risk fa ctors operate appear to be different.