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鞘内维生素 D、细胞因子与阿尔茨海默病核心生物标志物的相关性:一项横断面研究。

Associations Between Intrathecal Levels of Vitamin D, Cytokines, and Core Biomarkers of Alzheimer's Disease: A Cross-Sectional Study.

机构信息

Medical Department, Section of Geriatrics, Lovisenberg Diaconal Hospital, Oslo, Norway.

Faculty of Medicine, University of Oslo, Oslo, Norway.

出版信息

J Alzheimers Dis. 2022;89(3):825-834. doi: 10.3233/JAD-220407.

DOI:10.3233/JAD-220407
PMID:35938253
Abstract

BACKGROUND

Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer's disease (AD).

OBJECTIVE

In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-β, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls.

METHODS

We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-β, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups.

RESULTS

Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p = 0.01) and phosphorylated tau protein (p = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-β in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF.

CONCLUSION

Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein.

摘要

背景

多项研究已检验血清维生素 D 水平与认知之间的关联,但有关脑脊液(CSF)中维生素 D 水平及其与阿尔茨海默病(AD)之间关联的信息却鲜为人知。

目的

在这项横断面、探索性研究中,我们调查了 CSF 中维生素 D 与 AD 生物标志物、CSF 中的淀粉样β蛋白、tau 蛋白/磷酸化 tau 蛋白,以及 CSF 中的细胞因子 IL-6、IL-8 和 TNF-α之间的可能关联,这些标志物在认知障碍患者和认知健康对照者中均存在。

方法

我们纳入了 100 名年龄≥65 岁、因认知障碍评估而就诊的门诊患者和 76 名年龄和性别匹配的认知健康对照者。在两组人群中均分析了 CSF 中 25-羟维生素 D(25[OH]D)、淀粉样β蛋白、tau 蛋白和磷酸化 tau 蛋白以及 IL-6、IL-8 和 TNF-α的水平。

结果

所有组 CSF 中 25(OH)D 水平升高与 tau 蛋白(p=0.01)和磷酸化 tau 蛋白(p=0.005)水平降低相关。我们未发现 CSF 中 25(OH)D 水平与 CSF 中病理性淀粉样β蛋白水平以及 CSF 中 IL-6 或 TNF-α水平之间存在关联。CSF 中 25(OH)D 水平升高与 CSF 中 IL-8 水平升高相关(p=0.002)。然而,维生素 D 仅能解释 CSF 中 IL-8 变异的 6%。在 CSF 中 25(OH)D 与三种细胞因子之间的关联方面,患者组与对照组之间无显著差异。

结论

CSF 中 25(OH)D 水平较高的参与者其 CSF 中 tau 蛋白和磷酸化 tau 蛋白水平降低。

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