Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer's Disease Pathology and Neuronal Damage.
Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer's Disease Pathology and Neuronal Damage.
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DOI：
10.3233/jad-170602
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kramer JH
中科院分区：
文献类型：
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作者：
Bettcher BM;Johnson SC;Fitch R;Casaletto KB;Heffernan KS;Asthana S;Zetterberg H;Blennow K;Carlsson CM;Neuhaus J;Bendlin BB;Kramer JH
炎症标志物已被证明可以预测老年人的神经认知结果;然而，外周标志物反映中枢神经系统的程度仍然未知。我们研究了血浆和CSF炎症标志物之间的相关性，并探讨了这些标志物是否独立预测阿尔茨海默病（AD）病理或神经元损伤的CSF指标。在一组无症状老年人（n=173）中分析血浆和CSF样本的炎症标志物。分析CSF样本的AD病理学标志物（Aβ42、磷酸化tau [p-tau]、sAPP-β）或神经元损伤标志物（总tau;神经丝轻链[NFL]）（n=147）。对每种分析物进行单独的线性模型，同时输入CSF和血浆水平作为AD病理学或神经元损伤的预测因子和标志物作为结局指标。CSF和血浆MIP-1β水平之间存在强相关性，其余分析物存在中度相关性。关于AD病理学，血浆和CSF IL-8、CSF MIP-1β和CSF IP-10水平较高与p-tau水平较高相关。CSF IL-8水平升高与CSF Aβ1-42水平升高相关。较高的CSF sAPP-β水平仅与较高的血浆标志物（IL-8; MCP-1）相关。在神经元损伤方面，血浆和CSF IL-8、CSF IP-10和CSF MIP-1β水平较高与CSF总tau水平较高相关。探索性分析表明，CSF Aβ42改变了血浆炎症水平与CSF tau水平之间的关系。结果表明，血浆和CSF炎症标记物都独立地传递有关AD病理和神经元损伤的完整信息。
Inflammatory markers have been shown to predict neurocognitive outcomes in aging adults; however, the degree to which peripheral markers mirror the central nervous system remains unknown. We investigated the association between plasma and CSF markers of inflammation, and explored whether these markers independently predict CSF indicators of Alzheimer’s disease (AD) pathology or neuronal damage. Plasma and CSF samples were analyzed for inflammatory markers in a cohort of asymptomatic older adults (n=173). CSF samples were analyzed for markers of AD pathology (Aβ42, phosphorylated tau [p-tau], sAPP-β) or neuronal damage (total tau; neurofilament light chain [NFL])(n=147). Separate linear models for each analyte were conducted with CSF and plasma levels entered simultaneously as predictors and markers of AD pathology or neuronal damage as outcome measures. Strong associations were noted between CSF and plasma MIP-1β levels, and modest associations were observed for remaining analytes. With respect to AD pathology, higher levels of plasma and CSF IL-8, CSF MIP-1β, and CSF IP-10 were associated with higher levels of p-tau. Higher levels of CSF IL-8 were associated with higher levels of CSF Aβ1-42. Higher CSF sAPP-beta levels were associated with higher plasma markers only (IL-8; MCP-1). In terms of neuronal injury, higher levels of plasma and CSF IL-8, CSF IP-10, and CSF MIP-1β were associated with higher levels of CSF total tau. Exploratory analyses indicated that CSF Aβ42 modifies the relationship between plasma inflammatory levels and CSF tau levels. Results suggest that both plasma and CSF inflammatory markers independently relay integral information about AD pathology and neuronal damage.