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Association of blood-based DNA methylation markers with late-onset alzheimer disease: a potential diagnostic approach

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dc.contributor.authorAcha Santamaría, Blanca
dc.contributor.authorCorroza, Jon
dc.contributor.authorSánchez Ruiz de Gordoa, Javier
dc.contributor.authorCabello, Carolina
dc.contributor.authorRobles Solano, Maitane
dc.contributor.authorMéndez López, Iván
dc.contributor.authorMacías, Mónica
dc.contributor.authorZueco, Sara
dc.contributor.authorRoldán, Miren
dc.contributor.authorUrdánoz Casado, Amaya
dc.contributor.authorJericó Pascual, Ivonne
dc.contributor.authorErro Aguirre, María Elena
dc.contributor.authorAlcolea, Daniel
dc.contributor.authorLleo, Alberto
dc.contributor.authorBlanco Luquin, Idoia
dc.contributor.authorMendióroz Iriarte, Maite
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2024-04-26T14:43:29Z
dc.date.available2024-04-26T14:43:29Z
dc.date.issued2023
dc.date.updated2024-04-26T13:29:51Z
dc.description.abstractBackground and Objectives: There is an urgent need to identify novel noninvasive biomarkers for Alzheimer disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogenesis. Epigenetic biomarkers have been successfully implemented in other medical disciplines, such as oncology. The objective of this study was to explore the diagnostic accuracy of a blood-based DNA methylation marker panel as a noninvasive tool to identify patients with late-onset Alzheimer compared with age-matched controls. Methods: A case-control study was performed. Blood DNA methylation levels at 46 cytosine-guanine sites (21 genes selected after a comprehensive literature search) were measured by bisulfite pyrosequencing in patients with “probable AD dementia” following National Institute on Aging and the Alzheimer's Association guidelines (2011) and age-matched and sex-matched controls recruited at Neurology Department-University Hospital of Navarre, Spain, selected by convenience sampling. Plasma pTau181 levels were determined by Simoa technology. Multivariable logistic regression analysis was performed to explore the optimal model to discriminate patients with AD from controls. Furthermore, we performed a stratified analysis by sex. Results: The final study cohort consisted of 80 patients with AD (age: median [interquartile range] 79 [11] years; 58.8% female) and 100 cognitively healthy controls (age 77 [10] years; 58% female). A panel including DNA methylation levels at NXN, ABCA7, and HOXA3 genes and plasma pTau181 significantly improved (area under the receiver operating characteristic curve 0.93, 95% CI 0.89–0.97) the diagnostic performance of a single pTau181-based model, adjusted for age, sex, and APOE ɛ4 genotype. The sensitivity and specificity of this panel were 83.30% and 90.00%, respectively. After sex-stratified analysis, HOXA3 DNA methylation levels showed consistent association with AD. Discussion: These results highlight the potential translational value of blood-based DNA methylation biomarkers for noninvasive diagnosis of AD. Registration Information: Research Ethics Committee of the University Hospital of Navarre (PI17/02218).en
dc.description.sponsorshipSpanish Government through grants from the Institute of Health Carlos III (FIS PI17/02218), jointly funded by the European Regional Development Fund (ERDF), European Union, A way of shaping Europe; the Department of Industry of Government of Navarra (PI058 iBEAS-Plus and PI055 iBEAS-Plus); Institute of Health Carlos III (FIS PI20/01330 and AC19/00103 to AL) and CIBERNED (Program 1, Alzheimer Disease). The project leading to these results has received funding from la Caixa Foundation (ID 100010434) co-funded by Fundación Luzón (HR20-01109_BIOP-AD) under the project code LCF/PR/PR15/51100006.en
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dc.identifier.citationAcha, B., Corroza, J., Sánchez-Ruiz de Gordoa, J., Cabello, C., Robles, M., Méndez-López, I., Macías, M., Zueco, S., Roldan, M., Urdánoz-Casado, A., Jericó, I., Erro, M. E., Alcolea, D., Lleo, A., Blanco-Luquin, I., Mendioroz, M. (2023) Association of blood-based DNA methylation markers with late-onset alzheimer disease: A potential diagnostic approach. Neurology, 101(23), 234-247. https://doi.org/10.1212/WNL.0000000000207865.en
dc.identifier.doi10.1212/WNL.0000000000207865
dc.identifier.issn0028-3878
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/48041
dc.language.isoengen
dc.publisherLippincott Williams & Wilkinsen
dc.publisherAmerican Academy of Neurologyen
dc.relation.ispartofNeurology 2023, 101 (23), e2434-e2447en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F02218/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01330/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/AC19%2F00103/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//PI058 iBEAS-Plusen
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//PI055 iBEAS-Plusen
dc.relation.publisherversionhttps://doi.org/10.1212/WNL.0000000000207865
dc.rights© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBlood-based DNA methylation markersen
dc.subjectAlzheimer's diseaseen
dc.titleAssociation of blood-based DNA methylation markers with late-onset alzheimer disease: a potential diagnostic approachen
dc.typeinfo:eu-repo/semantics/article
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscoveryd09deda5-8d94-42e0-97f0-b32e34571988

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