Milanesi Elena, Dobre Maria, Cucos Cătălina Anca, Rojo Ana I, Jiménez-Villegas José, Capetillo-Zarate Estibaliz, Matute Carlos, Piñol-Ripoll Gerard, Manda Gina, Cuadrado Antonio
"Victor Babes" National Institute of Pathology, Bucharest, 050096, Romania.
Department of Endocrine Physiology and Nervous System, Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC, Madrid, 28029, Spain.
J Inflamm Res. 2021 Nov 20;14:6085-6102. doi: 10.2147/JIR.S334337. eCollection 2021.
Although Alzheimer's disease (AD) is associated with alterations of the central nervous system, this disease has an echo in blood that might represent a valuable source of biomarkers for improved diagnosis, prognosis and for monitoring drug response.
We performed a targeted transcriptomics study on 38 mild Alzheimer's disease (AD) patients and 38 matched controls for evaluating the expression levels of 136 inflammation and 84 redox genes in whole blood. Patients were diagnosed as mild AD based on altered levels of total TAU, phospho-TAU and Abeta in cerebrospinal fluid, and Abeta, Abeta and total TAU levels in plasma. Whenever possible, blood and brain comparisons were made using public datasets.
We found 48 inflammation and 34 redox genes differentially expressed in the blood of AD patients vs controls (FC >1.5, p < 0.01), out of which 22 pro-inflammatory and 12 redox genes exhibited FC >2 and p < 0.001. Receiver operating characteristic (ROC) analysis identified nine inflammation and seven redox genes that discriminated between AD patients and controls (area under the curve >0.9). Correlations of the dysregulated inflammation and redox transcripts indicated that may regulate several redox genes including and . Based on the gene expression profile, we have found that the master regulators of inflammation and redox homeostasis, NFκB and NRF2, were significantly disturbed in the blood of AD patients, as well as several zinc finger and helix-loop-helix transcription factors.
The selected inflammation and redox genes might be useful biomarkers for monitoring anti-inflammatory therapy in mild AD.
尽管阿尔茨海默病（AD）与中枢神经系统的改变有关，但这种疾病在血液中也有反映，这可能是用于改善诊断、预后以及监测药物反应的有价值的生物标志物来源。
我们对38例轻度阿尔茨海默病（AD）患者和38例匹配的对照进行了靶向转录组学研究，以评估全血中136个炎症基因和84个氧化还原基因的表达水平。根据脑脊液中总tau蛋白、磷酸化tau蛋白和β淀粉样蛋白水平的改变，以及血浆中β淀粉样蛋白、β淀粉样蛋白和总tau蛋白水平，将患者诊断为轻度AD。只要有可能，就使用公共数据集进行血液和大脑的比较。
我们发现48个炎症基因和34个氧化还原基因在AD患者血液与对照血液中差异表达（FC>1.5，p<0.01），其中22个促炎基因和12个氧化还原基因的FC>2且p<0.001。受试者工作特征（ROC）分析确定了9个炎症基因和7个氧化还原基因可区分AD患者和对照（曲线下面积>0.9）。失调的炎症和氧化还原转录本的相关性表明， 可能调节包括 和 在内的多个氧化还原基因。基于基因表达谱，我们发现炎症和氧化还原稳态的主要调节因子NFκB和NRF2在AD患者血液中显著紊乱，还有几个锌指和螺旋-环-螺旋转录因子也是如此。
所选的炎症和氧化还原基因可能是监测轻度AD抗炎治疗的有用生物标志物。
