Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
Exp Gerontol. 2020 Jul 15;136:110945. doi: 10.1016/j.exger.2020.110945. Epub 2020 Apr 11.
Inflammation plays a crucial role in Alzheimer's disease (AD). AD neurodegeneration and concurrent involvement of the peripheral immune system may promote leukocyte division and telomere shortening. We examined genotypes and plasma levels of two proinflammatory cytokines, IL-1beta and IL-18, and leukocyte telomere length (LTL) in patients with mild cognitive impairment (MCI) and AD. We wanted to determine whether changes in plasma IL-1beta and IL-18 levels, together with LTL shortening, could be diagnostic for disease progression from MCI to AD. Median plasma IL-1beta levels were in the order MCI patients (2.2 pg/ml) < AD patients (4.0 pg/ml), both of which differed significantly from the controls (0.0 pg/ml). In the AD patients, the lowest IL-1beta levels were associated with the presence of the C allele of IL-1beta rs16944 SNP. Median plasma IL-18 levels were in the order MCI patients (116.3 pg/ml) > AD patients (85.8 pg/ml), both of which were significantly higher than in the controls (17.6 pg/ml). Analysis of LTL showed a progressive reduction in the order controls > MCI > AD patients (p < 0.0001). Overall LTL reduction was correlated with increased plasma IL-1beta levels, substantiating the hypothesis that inflammatory processes secondary to neuroinflammation may trigger telomere attrition. Changes in plasma IL-1beta and Il-18 levels, and LTL seem to reflect shifts in AD stage; they may have potential use as blood biomarkers to monitor disease onset and progression from MCI to AD.
炎症在阿尔茨海默病（AD）中起着至关重要的作用。AD 神经退行性变和外周免疫系统的并发参与可能促进白细胞分裂和端粒缩短。我们检查了轻度认知障碍（MCI）和 AD 患者两种促炎细胞因子 IL-1β和 IL-18 的基因型和血浆水平，以及白细胞端粒长度（LTL）。我们想确定血浆 IL-1β和 IL-18 水平的变化以及 LTL 缩短是否可以诊断从 MCI 到 AD 的疾病进展。MCI 患者（2.2pg/ml）和 AD 患者（4.0pg/ml）的中位血浆 IL-1β水平均低于对照组（0.0pg/ml），差异均有统计学意义。在 AD 患者中，IL-1β rs16944 SNP 的 C 等位基因与最低的 IL-1β水平相关。MCI 患者（116.3pg/ml）的中位血浆 IL-18 水平高于 AD 患者（85.8pg/ml），差异均有统计学意义，均高于对照组（17.6pg/ml）。LTL 分析显示，按顺序，对照组> MCI> AD 患者的 LTL 逐渐减少（p<0.0001）。总体 LTL 减少与血浆 IL-1β水平升高相关，证实了炎症反应继发于神经炎症可能引发端粒磨损的假设。血浆 IL-1β和 Il-18 水平以及 LTL 的变化似乎反映了 AD 阶段的变化；它们可能作为血液生物标志物具有监测从 MCI 到 AD 的疾病发作和进展的潜力。
