APOE genotype and early β-amyloid accumulation in older adults without dementia

Objective: To clarify associations between APOE epsilon 4 allele and age on longitudinal rates of b-amyloid (Ab) accumulation within A beta+ and A beta-older individuals without dementia. Methods: We analyzed 595 older adults without dementia classified cross-sectionally as A beta- (n 5 325) and A beta+ (n 5 270) using longitudinal florbetapir PET. The influence of age and APOE genotype on longitudinal accumulation of Ab was examined with linear mixed models. Results: APOE epsilon 4 and older age were associated with higher risk of being classified as A beta+ at baseline. The annual rate of Ab accumulation was significantly greater than zero for A beta-epsilon 3 (0.0021 6 0.0007 standardized uptake value ratio [ SUVR] units) and A beta-epsilon 4 (0.0044 6 0.0010 SUVR units), as well as A beta+ epsilon 3 (0.0141 6 0.0019 SUVR units) and A beta+ epsilon 4 (0.0126 6 0.0018 SUVR units). Ab accumulation was significantly faster in A beta-epsilon 4 compared to A beta-epsilon 3 and A beta-epsilon 2. Rates of Ab accumulation did not differ significantly between A beta+ APOE groups. Older age was associated with higher rates of Ab accumulation in the A beta-group. Conclusions: APOE epsilon 4 carriage and older age were predictors of longitudinal Ab accumulation within the A beta-group but not the A beta+ group. APOE epsilon 2 carriage was protective against longitudinal Ab accumulation within the A beta-group. APOE genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting Ab accumulation before abnormal levels are reached.