Peripheral inflammatory biomarkers predict the deposition and progression of amyloid-β in cognitively unimpaired older adults.
Peripheral inflammatory biomarkers predict the deposition and progression of amyloid-β in cognitively unimpaired older adults.
复制标题
外周炎症生物标志物可预测认知未受损的老年人中β淀粉样蛋白的沉积和进展。
DOI：
10.1016/j.bbi.2021.03.015
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Snitz BE
中科院分区：
文献类型：
--
作者：
Oberlin LE;Erickson KI;Mackey R;Klunk WE;Aizenstein H;Lopresti BJ;Kuller LH;Lopez OL;Snitz BE
阿尔茨海默病(AD)的发病机制越来越多地与全身炎症有关，然而这种关系的机制和时间特异性却鲜为人知。我们的目标是描述老年认知正常(CU)成年人外周炎症生物标志物、认知和Aβ沉积之间的横断面和纵向关联。对139名CU老年人(平均年龄85.4岁(82-95岁))进行了神经心理测试、匹兹堡化合物B(PIB)-PET成像和结构MRI检查。分层回归模型分析了循环炎症生物标记物(白介素6、可溶性肿瘤坏死因子受体1和2、可溶性肿瘤坏死因子受体1和2、可溶性肿瘤坏死因子受体14、C反应蛋白)、认知和Aβ沉积之间的关系。临床前疾病的指数，包括病理性Aβ状态和海马体体积，被纳入评估条件相关性。在基线评估中，在那些海马区体积较小的患者中，IL-6和sTNFR2浓度较高与较大的全球Aβ负荷相关。在纵向模型中，IL-6预测随后转变为MCI，IL-6和C反应蛋白都预测全球和区域Aβ沉积的更大变化，特别是在基线水平PIB阳性的参与者中。这些关系经受住了人口统计学因素、抗高血压药物使用、糖尿病史、心脏病史、载脂蛋白Eε4携带者状态和脑白质损害的调整。在80岁及以上的CU成人的大样本中，外周炎症生物标志物与Aβ沉积的进展相关并预测其进展。这对于那些在基线时有临床前AD的生物标志物证据的人来说是特定的，支持最近的证据表明炎症表达谱有疾病状态依赖的差异。慢性、低水平的全身性炎症可能会加剧Aβ病理在那些有新出现疾病过程的人中的沉积，并将个人置于发生临床显著认知障碍的更高风险中。
Systemic inflammation has been increasingly implicated in the pathogenesis of Alzheimer’s disease (AD), yet the mechanistic and temporal specificity of this relationship is poorly understood. We aimed to characterize the cross-sectional and longitudinal associations between peripheral inflammatory biomarkers, cognition, and Aβ deposition in oldest-old cognitively unimpaired (CU) adults. A large sample of 139 CU older adults (mean age (range) = 85.4 (82–95)) underwent neuropsychological testing, Pittsburgh compound-B (PiB)-PET imaging and structural MRI. Hierarchical regression models examined associations between circulating inflammatory biomarkers (Interleukin-6 (IL-6), soluble Tumor Necrosis Factor receptors 1 and 2 (sTNFr1 and sTNFr2), soluble cluster of differentiation 14 (sCD14), C-reactive protein (CRP)), cognition, and global and regional Aβ deposition at baseline and over follow-up. Indices of preclinical disease, including pathologic Aβ status and hippocampal volume, were incorporated to assess conditional associations. At baseline evaluation, higher concentrations of IL-6 and sTNFr2 were associated with greater global Aβ burden in those with lower hippocampal volume. In longitudinal models, IL-6 predicted subsequent conversion to MCI and both IL-6 and CRP predicted greater change in global and regional Aβ deposition specifically among participants PiB-positive at baseline. These relationships withstood adjustment for demographic factors, anti-hypertensive medication use, history of diabetes, heart disease, APOE ε4 carrier status, and white matter lesions. In a large prospective sample of CU adults aged 80 and over, peripheral inflammatory biomarkers were associated with and predictive of the progression of Aβ deposition. This was specific to those with biomarker evidence of preclinical AD at baseline, supporting recent evidence of disease-state-dependent differences in inflammatory expression profiles. Chronic, low-level systemic inflammation may exacerbate the deposition of Aβ pathology among those with emerging disease processes, and place individuals at a higher risk of developing clinically significant cognitive impairment.
登录
查看更多内容
影响因子：
7.2
作者：
Choi, Hyo Jung;Byun, Min Soo;Lee, Dong Young
通讯作者：
Lee, Dong Young
影响因子：
4.2
作者：
Gao, Qi;Camous, Xavier;Ng, Tze-Pin
通讯作者：
Ng, Tze-Pin
影响因子：
4.8
作者：
Bradburn S;Sarginson J;Murgatroyd CA
通讯作者：
Murgatroyd CA
影响因子：
15.9
作者：
Aderka, D;Sorkine, P;Klausner, J
通讯作者：
Klausner, J
影响因子：
15.1
作者：
Beydoun, May A.;Weiss, Jordan;Zonderman, Alan B.
通讯作者：
Zonderman, Alan B.