To characterize the influence of apolipoprotein-E (APOE) genotype on cerebral Aβ load and longitudinal Aβ trajectories, [11C]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 [11C]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-ε4 was associated with increased Aβ burden and an earlier age of onset of Aβ positivity, whereas APOE-ε2 appeared to have modest protective effects against Aβ. APOE class did not predict rates of Aβ 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 Aβ positivity, although it is likely that other genetic, environmental, and lifestyle factors are important.

中文翻译：

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载脂蛋白-E 基因型对脑淀粉样蛋白负荷和纵向轨迹的影响

为了表征载脂蛋白-E (APOE) 基因型对脑 Aβ 负荷和纵向 Aβ 轨迹的影响，[11C] 匹兹堡化合物-B (PiB) 正电子发射断层扫描 (PET) 成像用于评估临床异质性队列中的淀粉样蛋白负荷428 名已知 APOE 基因型的老年参与者。使用串行 [11C] PiB 数据和重复测量模型对基于 APOE 基因型分类的 235 名参与者的子集的淀粉样蛋白轨迹进行建模。我们发现 APOE-ε4 与 Aβ 负荷增加和 Aβ 阳性发病年龄较早有关，而 APOE-ε2 似乎对 Aβ 具有适度的保护作用。APOE 类不能预测 Aβ 积累率。目前的研究表明，APOE 通过直接影响淀粉样蛋白生成过程来改变阿尔茨海默病的风险，