外周血管内皮功能障碍标志物与阿尔茨海默病相关的脑内生物标志物具有独立但累加的关系，并与功能障碍相关。
Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer's Disease.
机构信息
Alzheimer's Disease and Memory Disorders Center, Rhode Island Hospital, Providence, RI, USA.
Department of Neurology, Brown University Warren Alpert Medical School, Providence RI, USA.
出版信息
J Alzheimers Dis. 2021;80(4):1553-1565. doi: 10.3233/JAD-200759.
BACKGROUND
Cerebrovascular dysfunction confers risk for functional decline in Alzheimer's disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood.
OBJECTIVE
We utilized Alzheimer's Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD.
METHODS
Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis).
RESULTS
Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ42 (all < p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent.
CONCLUSION
Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.
背景
脑血管功能障碍会增加阿尔茨海默病（AD）患者功能下降的风险，但这两种致病过程的临床相互作用尚不清楚。
目的
我们利用阿尔茨海默病神经影像学倡议（ADNI）的数据，研究了外周衍生的可溶性细胞黏附分子（CAMs）与 AD 的临床诊断指标之间的关联。
方法
使用广义线性回归模型，我们在 ADNI 队列（n=112 例 AD，n=396 例轻度认知障碍（MCI），n=58 例认知正常）中检查了可溶性血浆血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和 E-选择素与基线诊断和功能障碍（临床痴呆评定总和评分，CDR-SB）的横断面关系。我们进一步分析了这些生物标志物与具有可用脑脊液（CSF）数据的亚组中脑为基础的 AD 生物标志物的关联（n=351）。线性回归的主效应和交互项得出的 p 值用于评估独立变量和因变量之间的关系是否有统计学意义（所有分析的显著水平均设定为 0.05 先验）。
结果
AD 组的平均 VCAM-1（p=0.0026）和 ICAM-1（p=0.0189）水平高于 MCI 组；然而，在 MCI 组和认知正常组之间没有差异。只有 VCAM-1 与 CDR-SB 评分相关（p=0.0157），APOE ɛ4 基因型对此有修饰作用。当 VCAM-1 与 CSF 淀粉样蛋白-β（Aβ42）、总 tau、磷酸化 tau（P-tau）或 P-tau/Aβ42（均<0.01）联合在 CDR-SB 模型中时，我们观察到独立的、累加的关联；ICAM-1 也呈现出类似的模式，但程度较小。
结论
我们的研究结果表明，血浆血管生物标志物和 CSF 生物标志物与 AD 相关的临床损害有独立关联。
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