Department of Cerebrovascular Disease, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
Transl Psychiatry. 2022 Mar 29;12(1):128. doi: 10.1038/s41398-022-01899-w.
Including apolipoprotein E-ε4 (APOE-ε4) status and older age into consideration may increase the accuracy of plasma Aβ/Aβ detecting Aβ+ individuals, but the rationale behind this remains to be fully understood. Besides, both Aβ pathology and vascular diseases are related to neurodegeneration and cognitive decline, but it is still not fully understood how APOE-ε4 modulates these relationships. In this study, we examined 241 non-demented Alzheimer's Disease Neuroimaging Initiative participants to investigate the associations among age, white matter hyperintensities (WMH), hypertension, hyperlipidemia, body mass index (BMI), plasma Aβ/Aβ measured by liquid chromatography tandem mass spectrometry, and F-florbetapir Aβ PET as well as their prediction of longitudinal adjusted hippocampal volume (aHCV) and cognition in APOE-ε4 carriers and non-carriers. We found older age predicted faster WMH increase (p = 0.024) and cortical Aβ accumulation (p = 0.043) in APOE-ε4 non-carriers only, whereas lower plasma Aβ/Aβ predicted faster cortical Aβ accumulation (p < 0.018) regardless of APOE-ε4 status. While larger WMH and underweight predicted (p < 0.05) faster decreases in aHCV and cognition in APOE-ε4 non-carriers, lower plasma Aβ/Aβ predicted (p < 0.031) faster decreases in aHCV and cognition in APOE-ε4 carriers. Higher Aβ PET also predicted faster rates of aHCV (p = 0.010) in APOE-ε4 carriers only, but was related to faster rates of cognitive decline (p < 0.022) regardless of APOE-ε4 status. These findings may provide novel insights into understanding different mechanisms underlie neurodegeneration and cognitive decline in non-demented elderly adults with and without APOE-ε4 allele, which may help the design of anti-Alzheimer's clinical trials.
将载脂蛋白 E-ε4（APOE-ε4）状态和年龄因素纳入考虑可能会提高血浆 Aβ/Aβ 检测到 Aβ+个体的准确性，但这背后的原理仍有待充分理解。此外，Aβ 病理学和血管疾病都与神经退行性变和认知能力下降有关，但目前仍不完全清楚 APOE-ε4 如何调节这些关系。在这项研究中，我们检查了 241 名非痴呆型阿尔茨海默病神经影像学倡议参与者，以研究年龄、脑白质高信号（WMH）、高血压、高血脂、体重指数（BMI）、液相色谱串联质谱法测定的血浆 Aβ/Aβ 与 F-氟比他滨 Aβ PET 之间的关联，以及它们对 APOE-ε4 携带者和非携带者的纵向调整海马体积（aHCV）和认知的预测。我们发现，在 APOE-ε4 非携带者中，年龄较大仅预测 WMH 增加（p=0.024）和皮质 Aβ 积累（p=0.043）更快，而较低的血浆 Aβ/Aβ 则预测皮质 Aβ 积累更快（p<0.018），无论 APOE-ε4 状态如何。较大的 WMH 和体重不足预测（p<0.05）APOE-ε4 非携带者的 aHCV 和认知功能下降更快，而较低的血浆 Aβ/Aβ 预测（p<0.031）APOE-ε4 携带者的 aHCV 和认知功能下降更快。APOE-ε4 携带者的 Aβ PET 水平较高也预测了 aHCV 更快的下降速度（p=0.010），但无论 APOE-ε4 状态如何，都与认知能力下降更快（p<0.022）有关。这些发现可能为理解非痴呆老年人群中有无 APOE-ε4 等位基因的神经退行性变和认知能力下降的不同机制提供新的见解，这可能有助于设计抗阿尔茨海默病的临床试验。
