San Diego State University/University of California, San Diego Joint Doctoral Program, San Diego.
Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
Alzheimers Dement. 2021 Jan;17(1):61-69. doi: 10.1002/alz.12173. Epub 2020 Sep 4.
Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition.
For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aβ) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aβ, including interactions with APOE ε4-carrier status.
Adjusting for tau PET, Aβ was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aβ PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in ε4-carriers, even among Aβ-negative individuals.
Findings suggest that APOE may interact with tau independently of Aβ and that elevated MTL tau confers negative cognitive consequences in Aβ-negative ε4 carriers.
载脂蛋白 E (APOE) 与阿尔茨海默病病理学相互作用，促进疾病进展。我们研究了 APOE 对淀粉样蛋白和 tau 正电子发射断层扫描 (PET) 与认知的独立关联的调节作用。
在来自阿尔茨海默病神经影像学倡议的 297 名认知正常的老年人中，回归方程模拟了认知与（1）皮质淀粉样蛋白 β (Aβ) PET 水平与 tau 调整，以及（2）内侧颞叶 (MTL) tau PET 水平与 Aβ 调整之间的关联，包括与 APOE ε4 携带者状态的相互作用。
在调整 tau PET 后，Aβ 与认知无关，也与 APOE 没有相互作用。相比之下，在调整 Aβ PET 后，MTL tau 与所有认知领域都有关联。此外，APOE 在 MTL tau 和 ε4 携带者记忆关联中的调节作用更强，即使在 Aβ 阴性个体中也是如此。
研究结果表明，APOE 可能与 tau 相互作用，而不依赖于 Aβ，并且升高的 MTL tau 在 Aβ 阴性的 ε4 携带者中会产生负面的认知后果。
