Campanelli Lorenzo, Galeano Pablo, Prestia Federico A, Cuesta Carolina, Dalmasso Maria C, Flores-López María, Gona Cristian, Irureta Nicolás, Kairiyama Claudia, Lisso Julieta, López-Gambero Antonio Jesús, Mintz Ines, Medel Nancy, Campuzano Karen S, Muchnik Carolina, Novack Gisela V, Olivar Natividad, Quiroga Ivana, Requena-Ocaña Nerea, Reyes-Bueno Jose Antonio, Serrano-Castro Pedro, Sevillano Zulma, Solis Patricia, Suárez Juan, Villella Ivana, Wukitsevits Nancy, Castaño Eduardo M, Taragano Fernando, Kochen Silvia, Politis Daniel G, Brusco Luis I, Rodríguez de Fonseca Fernando, Morelli Laura
Laboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, Argentina.
Hospital Interzonal General de Agudos (HIGA) Eva Perón, Av. 101 Dr. Ricardo Balbín 3200, Provincia de Buenos Aires, Buenos Aires, B1650NBN, Argentina.
Heliyon. 2025 Jan 9;11(2):e41725. doi: 10.1016/j.heliyon.2025.e41725. eCollection 2025 Jan 30.
Inflammation and angiogenesis have been defined as potential mechanisms associated with clinical progression from a cognitively normal state to Alzheimer's disease (AD). In this observational case-control study, we aimed to determine plasma levels of cytokines as indicators of inflammation involved in cognitive decline. We measured 30 plasma proteins in 49 controls (CTL), 36 individuals with mild cognitive impairment (MCI) and 52 patients diagnosed with probable AD. After applying strict filters for quantification limits, only 13 analytes were included in the analysis. Kruskal-Wallis tests showed significant differences between diagnostic groups for nine cytokines (IL-16, IL-7, VEGF, IL-8, eotaxin, MCP-1, MCP-4, MDC and TARC). Non-parametric MANCOVA showed that sex and diagnosis affected cytokine levels in the blood. To determine the sensitivity and specificity of the markers, we performed receiver operating characteristic (ROC) curve analysis. Only those analytes that showed an area under the curve (AUC) ≥ 0.70 were included in the multivariate logistic regression models to better understand the contribution of cytokines to clinical status. Three models: 1) CTL vs. AD; 2) CTL vs. MCI, and 3) MCI vs. AD were developed, with sex and age as covariates. In each model, two cytokines remained significantly different (model 1: IL-16 and MDC; model 2: eotaxin and MDC and model 3: IL-7 and VEGF). Taken together, this report identifies a set of plasma markers of inflammation and strengthens the role of glial biology in different clinical stages of AD.
炎症和血管生成已被确定为与从认知正常状态向阿尔茨海默病（AD）临床进展相关的潜在机制。在这项观察性病例对照研究中，我们旨在确定细胞因子的血浆水平，作为参与认知衰退的炎症指标。我们测量了49名对照者（CTL）、36名轻度认知障碍（MCI）个体和52名被诊断为可能患有AD的患者的30种血浆蛋白。在对定量限应用严格筛选后，分析中仅纳入了13种分析物。Kruskal-Wallis检验显示，9种细胞因子（IL-16、IL-7、VEGF、IL-8、嗜酸性粒细胞趋化因子、MCP-1、MCP-4、MDC和TARC）在诊断组之间存在显著差异。非参数MANCOVA显示，性别和诊断会影响血液中的细胞因子水平。为了确定这些标志物的敏感性和特异性，我们进行了受试者工作特征（ROC）曲线分析。只有那些曲线下面积（AUC）≥0.70的分析物才被纳入多变量逻辑回归模型，以更好地了解细胞因子对临床状态的贡献。构建了三个模型：1）CTL与AD；2）CTL与MCI；3）MCI与AD，并将性别和年龄作为协变量。在每个模型中，两种细胞因子仍存在显著差异（模型1：IL-16和MDC；模型2：嗜酸性粒细胞趋化因子和MDC；模型3：IL-7和VEGF）。综上所述，本报告确定了一组炎症的血浆标志物，并强化了神经胶质生物学在AD不同临床阶段的作用。
