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

Lachén Montes, Mercedes; Íñigo-Marco, Ignacio; Cartas Cejudo, Paz; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique

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.author	Lachén Montes, Mercedes
dc.contributor.author	Íñigo-Marco, Ignacio
dc.contributor.author	Cartas Cejudo, Paz
dc.contributor.author	Fernández Irigoyen, Joaquín
dc.contributor.author	Santamaría Martínez, Enrique
dc.contributor.department	Ciencias de la Salud	es_ES
dc.contributor.department	Osasun Zientziak	eu
dc.contributor.funder	Gobierno de Navarra / Nafarroako Gobernua	es
dc.date.accessioned	2022-01-11T09:29:23Z
dc.date.available	2022-01-11T09:29:23Z
dc.date.issued	2021
dc.description.abstract	The 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.sponsorship	This 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.extent	18 p.
dc.format.mimetype	application/pdf	en
dc.identifier.doi	10.3390/jpm11060503
dc.identifier.issn	2075-4426
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/41691
dc.language.iso	eng	en
dc.publisher	MDPI
dc.relation.ispartof	Journal of Personalized Medicine, 11 (6)
dc.relation.projectID	info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/
dc.relation.publisherversion	http://doi.org/10.3390/jpm11060503
dc.rights	© 2021 by the authors. Creative Commons Attribution	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Alzheimer’s disease	en
dc.subject	Mixed dementia	en
dc.subject	Olfactory bulb	en
dc.subject	Proteomics	en
dc.subject	Vascular dementia	en
dc.title	Olfactory bulb proteomics reveals widespread proteostatic disturbances in mixed dementia and guides for potential serum biomarkers to discriminate alzheimer disease and mixed dementia phenotypes	en
dc.type	info:eu-repo/semantics/article
dc.type.version	info:eu-repo/semantics/publishedVersion
dspace.entity.type	Publication
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