Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease

Abstract

Elena Milanesi,1,* Maria Dobre,1,* Cătălina Anca Cucos,1 Ana I Rojo,2– 5 José Jiménez-Villegas,2,3 Estibaliz Capetillo-Zarate,5– 7 Carlos Matute,6,7 Gerard Piñol-Ripoll,8 Gina Manda,1 Antonio Cuadrado1– 5 1“Victor Babes” National Institute of Pathology, Bucharest, 050096, Romania; 2Department of Endocrine Physiology and Nervous System, Instituto de Investigaciones Biomédicas “Alberto Sols” UAM-CSIC, Madrid, 28029, Spain; 3Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, 28049, Spain; 4Neuroscience Section, Instituto de Investigación Sanitaria La Paz (IDIPAZ), Madrid, 28046, Spain; 5Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid, 28031, Spain; 6IKERBASQUE, Basque Foundation for Science, Bilbao, 48009, Spain; 7Department of Neuroscience, University of the Basque Country UPV/EHU, Achucarro Basque Center for Neuroscience, Leioa, Spain; 8Unitat Trastons Cognitius, Hospital Universitari Santa Maria-IRB Leida, Lleida, 25198, Spain*These authors contributed equally to this workCorrespondence: Antonio CuadradoInstituto de Investigaciones Biomédicas “Alberto Sols” UAM-CSIC, C/ Arturo Duperier 4, Madrid, 28029, SpainEmail [email protected] Manda“Victor Babes” National Institute of Pathology, 99-101 Splaiul Independentei, Bucharest, 050096, RomaniaEmail [email protected]: 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.Methods: 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(1– 42) in cerebrospinal fluid, and Abeta(1– 40), Abeta(1– 42) and total TAU levels in plasma. Whenever possible, blood and brain comparisons were made using public datasets.Results: We found 48 inflammation and 34 redox genes differentially expressed in the blood of AD patients vs controls (FC > 1.5, p 2 and p 0.9). Correlations of the dysregulated inflammation and redox transcripts indicated that RELA may regulate several redox genes including DUOX1 and GSR. 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.Conclusion: The selected inflammation and redox genes might be useful biomarkers for monitoring anti-inflammatory therapy in mild AD.Keywords: oxidative stress, neuroinflammation, gene expression, dementia, NRF2, NFkappaB

Keywords

• oxidative stress
• neuroinflammation
• gene expression
• dementia
• nrf2
• nfkappab.