白细胞介素-1β、白细胞介素-6、白细胞介素-10 和肿瘤坏死因子-α的单核苷酸多态性与人类阿尔茨海默病病理易感性有关。
IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer's Disease Pathology.
机构信息
Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
Department of Molecular Medicine, Institute Ruđer Bošković, Zagreb, Croatia.
出版信息
J Alzheimers Dis. 2020;75(3):1029-1047. doi: 10.3233/JAD-200056.
BACKGROUND
Neuroinflammation plays an important role in Alzheimer's disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor α (TNFα) that participate in neuron damage, but also anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response. Previous studies showed the association of IL-1α -889C/T (rs1800587), IL-1β-1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896), and TNFα -308A/G (rs1800629) polymorphisms with AD.
OBJECTIVE
We aimed to investigate whether people with certain IL-1α, IL-1β, IL-6, IL-10, and TNFα genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-β1-42, total tau (t-tau), tau phosphorylated at Thr 181 (p-tau181), Ser 199 (p-tau199), and Thr 231 (p-tau231), and visinin-like protein 1 (VILIP-1).
METHODS
The study included 115 AD patients, 53 patients with mild cognitive impairment, and 11 healthy controls. The polymorphisms were determined using real-time polymerase chain reaction. Levels of CSF biomarkers were determined by enzyme-linked immunosorbent assay.
RESULTS
A significant increase in p-tau CSF levels was found in patients with the AA IL-10 -1082G/A and GG TNFα -308A/G genotypes, and in carriers of a G allele in IL-1β -1473C/G and IL-6 -174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1β -1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β -1473C/G, GC IL-6 -174C/G, and GG TNFα -308A/G genotype.
CONCLUSION
These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1β (1473C/G), IL6 (-174C/G), and TNFIα (-308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.
背景
神经炎症在阿尔茨海默病（AD）中起着重要作用。在此过程中，活化的小胶质细胞释放促炎细胞因子，如白细胞介素（IL）-1α、IL-1β、IL-6 和肿瘤坏死因子 α（TNFα），这些细胞因子参与神经元损伤，但也有抗炎细胞因子（如 IL-10），它们维持免疫反应的稳态。先前的研究表明，IL-1α-889C/T（rs1800587）、IL-1β-1473G/C（rs1143623）、IL-6-174C/G（rs1800795）、IL-10-1082G/A（rs1800896）和 TNFα-308A/G（rs1800629）多态性与 AD 有关。
目的
我们旨在研究这些多态性中特定的 IL-1α、IL-1β、IL-6、IL-10 和 TNFα 基因型的个体是否更容易发展为 AD 相关的病理，这反映在脑脊液（CSF）AD 生物标志物的病理水平上，包括淀粉样蛋白-β1-42、总 tau（t-tau）、tau 磷酸化 Thr181（p-tau181）、Ser199（p-tau199）和 Thr231（p-tau231）以及 visinin-like 蛋白 1（VILIP-1）。
方法
该研究纳入了 115 名 AD 患者、53 名轻度认知障碍患者和 11 名健康对照者。采用实时聚合酶链反应法确定多态性。采用酶联免疫吸附试验测定 CSF 生物标志物水平。
结果
AA 型 IL-10-1082G/A 和 GG 型 TNFα-308A/G 基因型患者的 p-tau CSF 水平显著升高，IL-1β-1473C/G 和 IL-6-174C/G 多态性中携带 G 等位基因的患者 t-tau 水平升高。IL-1β-1473C/G 多态性中携带 G 等位基因的患者 VILIP-1 水平升高。IL-1β-1473C/G 中 CG 和 GG 型、IL-6-174C/G 中 GC 型和 TNFα-308A/G 中 GG 型患者 VILIP-1 水平升高。
结论
这些结果表明，携带特定基因型的个体在 IL10（-1082G/A）、IL1β（1473C/G）、IL6（-174C/G）和 TNFIα（-308A/G）中可能更容易发生神经炎症，进而发展为 AD。
Zotero 插件