Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition

Neocortical A beta-amyloid deposition, one of the hallmark pathologic features of Alzheimer's disease (AD), begins decades prior to the presence of clinical symptoms. As clinical trials move to secondary and even primary prevention, understanding the rates of neocortical A beta-amyloid deposition and the age at which A beta-amyloid deposition becomes abnormal is crucial for optimizing the timing of these trials. As APOE-epsilon 4 carriage is thought to modulate the age of clinical onset, it is also important to understand the impact of APOE-epsilon 4 carriage on the age at which the neocortical A beta-amyloid deposition becomes abnormal. Here, we show that, for 455 participants with over 3 years of follow-up, abnormal levels of neocortical A beta-amyloid were reached on average at age 72 (66.5-77.1). The APOE-epsilon 4 carriers reached abnormal levels earlier at age 63 (59.6-70.3); however, noncarriers reached the threshold later at age 78 (76.1-84.4). No differences in the rates of deposition were observed between APOE-epsilon 4 carriers and noncarriers after abnormal A beta-amyloid levels had been reached. These results suggest that primary and secondary prevention trials, looking to recruit at the earliest stages of disease, should target APOE-epsilon 4 carriers between the ages of 60 and 66 and noncarriers between the ages of 76 and 84. (C) 2020 Elsevier Inc. All rights reserved.