APOE genotype and early β-amyloid accumulation in older adults without dementia
APOE genotype and early β-amyloid accumulation in older adults without dementia
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DOI：
10.1212/wnl.0000000000004336
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发表时间：
2017-09-05
期刊：
影响因子：
9.9
通讯作者：
Mormino, Elizabeth C.
中科院分区：
文献类型：
--
作者：
Lim, Yen Ying;Mormino, Elizabeth C.
目的：阐明 APOE epsilon 4 等位基因和年龄与 Aβ+ 和 Aβ- 未患痴呆症的老年人体内 b-淀粉样蛋白 (Ab) 纵向积累率之间的关系。方法：我们使用纵向氟倍吡酯 PET 分析了 595 名未患有痴呆症的老年人，将其横断面分类为 Aβ-（n 5 325）和 Aβ+（n 5 270）。使用线性混合模型检查了年龄和 APOE 基因型对 Ab 纵向积累的影响。结果：APOE epsilon 4 和年龄较大与基线时被分类为 A beta+ 的较高风险相关。 A beta-epsilon 3（0.0021 6 0.0007 标准化摄取值比 [SUVR] 单位）和 A beta-epsilon 4（0.0044 6 0.0010 SUVR 单位）以及 A beta+ epsilon 3（0.0141 6 0.0019 SUVR 单位）和 A beta+ epsilon 4 的年抗体积累率显着大于零（0.0126 6 0.0018 SUVR 单位）。与 A beta-epsilon 3 和 A beta-epsilon 2 相比，A beta-epsilon 4 中的 Ab 积累明显更快。Aβ+ APOE 组之间的 Ab 积累率没有显着差异。年龄较大与 A β 组中抗体积累率较高相关。结论：APOE epsilon 4 携带和年龄较大是 A β 组内纵向抗体积累的预测因素，但不是 A β+ 组中的预测因素。 APOE epsilon 2 携带可防止 A β 组内纵向抗体积累。 APOE 基因型与实际年龄相结合可能有助于一级预防试验的参与者选择，目的是在达到异常水平之前阻止抗体积累。
Objective: To clarify associations between APOE epsilon 4 allele and age on longitudinal rates of b-amyloid (Ab) accumulation within A beta+ and A beta-older individuals without dementia.Methods: We analyzed 595 older adults without dementia classified cross-sectionally as A beta- (n 5 325) and A beta+ (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 epsilon 4 and older age were associated with higher risk of being classified as A beta+ at baseline. The annual rate of Ab accumulation was significantly greater than zero for A beta-epsilon 3 (0.0021 6 0.0007 standardized uptake value ratio [ SUVR] units) and A beta-epsilon 4 (0.0044 6 0.0010 SUVR units), as well as A beta+ epsilon 3 (0.0141 6 0.0019 SUVR units) and A beta+ epsilon 4 (0.0126 6 0.0018 SUVR units). Ab accumulation was significantly faster in A beta-epsilon 4 compared to A beta-epsilon 3 and A beta-epsilon 2. Rates of Ab accumulation did not differ significantly between A beta+ APOE groups. Older age was associated with higher rates of Ab accumulation in the A beta-group.Conclusions: APOE epsilon 4 carriage and older age were predictors of longitudinal Ab accumulation within the A beta-group but not the A beta+ group. APOE epsilon 2 carriage was protective against longitudinal Ab accumulation within the A beta-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.