Neocortical Aβ-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 Aβ-amyloid deposition and the age at which Aβ-amyloid deposition becomes abnormal is crucial for optimizing the timing of these trials. As APOE-ε4 carriage is thought to modulate the age of clinical onset, it is also important to understand the impact of APOE-ε4 carriage on the age at which the neocortical Aβ-amyloid deposition becomes abnormal. Here, we show that, for 455 participants with over 3 years of follow-up, abnormal levels of neocortical Aβ-amyloid were reached on average at age 72 (66.5-77.1). The APOE-ε4 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-ε4 carriers and noncarriers after abnormal Aβ-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-ε4 carriers between the ages of 60 and 66 and noncarriers between the ages of 76 and 84.

中文翻译：

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APOE-ε4 携带对新皮质 Aβ-淀粉样蛋白沉积的发生和速率的影响

新皮质 Aβ-淀粉样蛋白沉积是阿尔茨海默病 (AD) 的标志性病理特征之一，在临床症状出现前几十年就开始了。随着临床试验转向二级甚至一级预防，了解新皮质 Aβ-淀粉样蛋白沉积的速度和 Aβ-淀粉样蛋白沉积异常的年龄对于优化这些试验的时间安排至关重要。由于 APOE-ε4 携带被认为会调节临床发病年龄，因此了解 APOE-ε4 携带对新皮质 Aβ-淀粉样蛋白沉积异常年龄的影响也很重要。在这里，我们表明，对于 455 名随访超过 3 年的参与者，平均在 72 岁 (66.5-77.1) 时达到了异常水平的新皮质 Aβ-淀粉样蛋白。APOE-ε4 携带者在 63 岁（59.6-70.3）时较早达到异常水平；然而，非携带者在 78 岁 (76.1-84.4) 时达到了阈值。在达到异常 Aβ-淀粉样蛋白水平后，在 APOE-ε4 载体和非载体之间没有观察到沉积速率的差异。这些结果表明，希望在疾病的最早阶段招募的一级和二级预防试验应针对 60 至 66 岁之间的 APOE-ε4 携带者和 76 至 84 岁之间的非携带者。