Olfactory bulb proteomics reveals widespread proteostatic disturbances in mixed dementia and guides for potential serum biomarkers to discriminate alzheimer disease and mixed dementia phenotypes

dc.contributor.authorLachén Montes, Mercedes
dc.contributor.authorÍñigo-Marco, Ignacio
dc.contributor.authorCartas Cejudo, Paz
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-01-11T09:29:23Z
dc.date.available2022-01-11T09:29:23Z
dc.date.issued2021
dc.description.abstractThe most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer's disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related dementias, little is known about the impact of this sensorial impairment in MixD at the molecular level. To address this gap in knowledge, we assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n = 6) respect to neurologically intact controls (n = 7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolism, and neuron projection regeneration. In addition, network-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT, and the PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, also being deregulated across different tauopathies, synucleinopathies, and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory pro-teomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phenotypes.en
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministry of Science, Innovation and Universities (Ref. PID2019-110356RB-I00/AEI/10.13039/501100011033) and the Department of Economic and Business Development from Government of Navarra (Ref. 0011-1411-2020-000028 to E.S.).en
dc.format.extent18 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.3390/jpm11060503
dc.identifier.issn2075-4426
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/41691
dc.language.isoengen
dc.publisherMDPI
dc.relation.ispartofJournal of Personalized Medicine, 11 (6)
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/
dc.relation.publisherversionhttp://doi.org/10.3390/jpm11060503
dc.rights© 2021 by the authors. Creative Commons Attributionen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer’s diseaseen
dc.subjectMixed dementiaen
dc.subjectOlfactory bulben
dc.subjectProteomicsen
dc.subjectVascular dementiaen
dc.titleOlfactory bulb proteomics reveals widespread proteostatic disturbances in mixed dementia and guides for potential serum biomarkers to discriminate alzheimer disease and mixed dementia phenotypesen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationcc02d7db-8e88-40d1-81e0-834617b4849d
relation.isAuthorOfPublicationda1d0e22-8279-4c6c-a7c5-cef564dc9542
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscoverycc02d7db-8e88-40d1-81e0-834617b4849d

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