Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration
Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration
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DOI：
10.1016/j.neurobiolaging.2018.11.001
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发表时间：
2019-03-01
影响因子：
4.2
通讯作者：
Lee, Dong Young
中科院分区：
文献类型：
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作者：
Jeon, So Yeon;Byun, Min Soo;Lee, Dong Young
本研究旨在探讨高血压与 β-淀粉样蛋白 (Ab beta) 和阿尔茨海默病 (AD) 神经变性生物标志物的关系以及载脂蛋白 E-ε 4 (APOE4) 的调节作用。总共有 259 名认知正常 (CN) 和 79 名 AD 痴呆老年人接受了临床评估，包括评估是否存在高血压、[C-11]-匹兹堡化合物-B-正电子发射断层扫描、磁共振成像和 APOE 基因分型。我们采用了临床阶段特定的方法，分别关注 CN 和 AD 痴呆阶段。对于 CN 组，与没有高血压的人相比，患有高血压的人表现出 AD 特征皮质厚度减少。随后的亚组分析表明，仅在 APOE4 非携带者中，高血压与 AD 特征皮质厚度减少相关，而在 APOE4 携带者中，高血压与 Aβ 沉积升高相关。同时，无论APOE4状态如何，患有高血压的AD痴呆患者的Aβ沉积均显着低于不患有高血压的患者。总之，研究结果表明，高血压主要通过减少大脑储备来导致 AD。然而，对于 APOE4 携带者来说，高血压似乎还通过淀粉样蛋白依赖性途径促进 AD 过程。 (C) 2018 Elsevier Inc. 保留所有权利。
This study aimed to investigate the relationship of hypertension with beta-amyloid (Ab beta) and neuro-degeneration biomarkers of Alzheimer's disease (AD) and the modulating effect of apolipoprotein E-epsilon 4 (APOE4). In total, 259 cognitively normal (CN) and 79 AD dementia older adults received clinical assessments including the evaluation for the presence of hypertension, [C-11]-Pittsburgh-compound-B-positron emission tomography, magnetic resonance imaging, and APOE genotyping. We used a clinical stage-specific approach, separately focusing on CN and AD dementia stages. For the CN group, individuals with hypertension showed reduced AD signature cortical thickness compared with those without hypertension. Subsequent subgroup analyses showed that hypertension was associated with reduced AD signature cortical thickness only in APOE4 noncarriers, whereas hypertension was associated with elevated A beta deposition in APOE4 carriers. Meanwhile, regardless of APOE4 status, AD dementia patients with hypertension had significantly lower A beta deposition than those without hypertension. In conclusion, the findings suggest that hypertension contributes to AD primarily through the reduction of brain reserve. In case of APOE4 carriers, however, hypertension seems to additionally facilitate AD process through amyloid-dependent pathway. (C) 2018 Elsevier Inc. All rights reserved.