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

Lim, Yen Ying; Mormino, Elizabeth C; Stern, Yaakov; Alzheimer's Disease Neuroimaging Initiative

Objective: To clarify associations between APOE e4 allele and age on longitudinal rates of b-amyloid (Ab) accumulation within Ab1 and Ab2 older individuals without dementia. Methods: We analyzed 595 older adults without dementia classified cross-sectionally as Ab2 (n 5 325) and Ab1 (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 e4 and older age were associated with higher risk of being classified as Ab1 at baseline. The annual rate of Ab accumulation was significantly greater than zero for Ab2 e3 (0.0021 6 0.0007 standardized uptake value ratio [SUVR] units) and Ab2 e4 (0.0044 6 0.0010 SUVR units), as well as Ab1 e3 (0.0141 6 0.0019 SUVR units) and Ab1 e4 (0.0126 6 0.0018 SUVR units). Ab accumulation was significantly faster in Ab2 e4 compared to Ab2 e3 and Ab2 e2. Rates of Ab accumulation did not differ significantly between Ab1 APOE groups. Older age was associated with higher rates of Ab accumulation in the Ab2 group. Conclusions: APOE e4 carriage and older age were predictors of longitudinal Ab accumulation within the Ab2 group but not the Ab1 group. APOE e2 carriage was protective against longitudinal Ab accumulation within the Ab2 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. Neurology® 2017;89:1028–1034



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February 11, 2022