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

Background: 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 tran...

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Autores: Milanesi, Elena, Dobre, Maria, Cucos, Catalina Anca, Rojo, Ana I., Jiménez Villegas, José, Capetillo González de Zárate, Estíbaliz, Matute Almau, Carlos José, Piñol Ripoll, Gerard, Manda, Gina, Cuadrado, Antonio
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/70770
Acceso en línea:http://hdl.handle.net/10810/70770
Access Level:acceso abierto
Palabra clave:oxidative stress
neuroinflammation
gene expression
dementia
NRF2
NFkappaB
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spelling Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s DiseaseMilanesi, ElenaDobre, MariaCucos, Catalina AncaRojo, Ana I.Jiménez Villegas, JoséCapetillo González de Zárate, EstíbalizMatute Almau, Carlos JoséPiñol Ripoll, GerardManda, GinaCuadrado, Antoniooxidative stressneuroinflammationgene expressiondementiaNRF2NFkappaBBackground: 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 inflam mation 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 < 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 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.Dovepress202420242021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/70770reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.dovepress.com/whole-blood-expression-pattern-of-inflammation-and-redox-genes-in-mild-peer-reviewed-fulltext-article-JIRinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc/3.0/© 2021 Milanesi et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/).oai:addi.ehu.eus:10810/707702026-06-18T09:23:17Z
dc.title.none.fl_str_mv Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
title Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
spellingShingle Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
Milanesi, Elena
oxidative stress
neuroinflammation
gene expression
dementia
NRF2
NFkappaB
title_short Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
title_full Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
title_fullStr Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
title_full_unstemmed Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
title_sort Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer’s Disease
dc.creator.none.fl_str_mv Milanesi, Elena
Dobre, Maria
Cucos, Catalina Anca
Rojo, Ana I.
Jiménez Villegas, José
Capetillo González de Zárate, Estíbaliz
Matute Almau, Carlos José
Piñol Ripoll, Gerard
Manda, Gina
Cuadrado, Antonio
author Milanesi, Elena
author_facet Milanesi, Elena
Dobre, Maria
Cucos, Catalina Anca
Rojo, Ana I.
Jiménez Villegas, José
Capetillo González de Zárate, Estíbaliz
Matute Almau, Carlos José
Piñol Ripoll, Gerard
Manda, Gina
Cuadrado, Antonio
author_role author
author2 Dobre, Maria
Cucos, Catalina Anca
Rojo, Ana I.
Jiménez Villegas, José
Capetillo González de Zárate, Estíbaliz
Matute Almau, Carlos José
Piñol Ripoll, Gerard
Manda, Gina
Cuadrado, Antonio
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv oxidative stress
neuroinflammation
gene expression
dementia
NRF2
NFkappaB
topic oxidative stress
neuroinflammation
gene expression
dementia
NRF2
NFkappaB
description Background: 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 inflam mation 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 < 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 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/70770
url http://hdl.handle.net/10810/70770
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.dovepress.com/whole-blood-expression-pattern-of-inflammation-and-redox-genes-in-mild-peer-reviewed-fulltext-article-JIR
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc/3.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/3.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Dovepress
publisher.none.fl_str_mv Dovepress
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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