Influence of apolipoprotein-E genotype on brain amyloid load and longitudinal trajectories

To characterize the influence of apolipoprotein-E (APOE) genotype on cerebral A beta load and longitudinal A beta trajectories, [C-11]Pittsburgh compound-B (PiB) positron emission tomography (PET) imaging was used to assess amyloid load in a clinically heterogeneous cohort of 428 elderly participants with known APOE genotype. Serial [C-11 epsilon]PiB data and a repeated measures model were used to model amyloid trajectories in a subset of 235 participants classified on the basis of APOE genotype. We found that APOE-epsilon 4 was associated with increased A beta burden and an earlier age of onset of A beta positivity, whereas APOE-epsilon 2 appeared to have modest protective effects against A beta. APOE class did not predict rates of A beta accumulation. The present study suggests that APOE modifies Alzheimer's disease risk through a direct influence on amyloidogenic processes, which manifests as an earlier age of onset of A beta positivity, although it is likely that other genetic, environmental, and lifestyle factors are important. (C) 2020 Elsevier Inc. All rights reserved.