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Amyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in Alzheimer’s disease

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dc.contributor.authorCuadrado-Tejedor, Mar
dc.contributor.authorPérez-González, Marta
dc.contributor.authorAlfaro-Ruiz, Rocío
dc.contributor.authorBadesso, Sara
dc.contributor.authorSucunza, Diego
dc.contributor.authorEspelosín, María
dc.contributor.authorUrsúa, Susana
dc.contributor.authorLachén Montes, Mercedes
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorLuján, Rafael
dc.contributor.authorGarcía-Osta, Ana
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-04-05T11:01:07Z
dc.date.available2022-04-05T11:01:07Z
dc.date.issued2021
dc.description.abstractDespite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer’s disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9) carrying the mutant P301L form of human tau, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or wild type mice (WT). Three months after injections, memory tasks, biochemical and immunohistochemical analysis were performed. We found that the overexpression of hTauP301L accelerates memory deficits in APP/PS1 mice, but it did not affect memory function of WT mice. Likewise, biochemical assays showed that only in the case of APP/PS1-hTauP301L injected mice, an important accumulation of tau was observed in the insoluble urea fraction. Similarly, electron microscopy images revealed that numerous clusters of tau immunoparticles appear at the dendrites of APP/PS1 injected mice and not in WT animals, suggesting that the presence of amyloid is necessary to induce tau aggregation. Interestingly, these tau immunoparticles accumulate in dendritic mitochondria in the APP/PS1 mice, whereas most of mitochondria in WT injected mice remain free of tau immunoparticles. Taken together, it seems that amyloid induces tau aggregation and accumulation in the dendritic mitochondria and subsequently may alter synapse function, thus, contributing to accelerate cognitive decline in APP/PS1 mice.en
dc.description.sponsorship) to J.F.-I. and E.S and from the Department of Economic and Business Development from Government of Navarra (INNOLFACT project; Ref. 0011-1411-2020-000028).We gratefully acknowledge grant funding support from Ministry of Science and Innovation (MINECO) with exp. PID2019-104921RB-I00/MCI/AEI/10.13039/501100011033as well as to the Foundation for Applied Medical Research, the University of Navarra (Pamplona, Spain) for financial support and the Asociación de Amigos of the University of Navarra for the grant to M.P.-G. and S.B. We also gratefully acknowledge grant funding support from Spanish Ministerio de Economía y Competitividad (RTI2018-095812-B-I00 MCIN/ AEI/10.13039/501100011033) y por FEDER una manera de hacer Europa and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229) to RL, from the Spanish Ministry of Science Innovation and Universities (Ref. PID2019-110356RB-I00/AEI/10.13039/501100011033
dc.format.extent17 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.3390/ijms222111950
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/42652
dc.language.isoengen
dc.publisherMDPI
dc.relation.ispartofInternational Journal of Molecular Sciences, 22 (21)en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104921RB-I00/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095812-B-I00/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/en
dc.relation.publisherversionhttps://doi.org/10.3390/ijms222111950
dc.rights© 2021 by the authors. Creative Commons Attribution 4.0 Internationalen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer’s diseaseen
dc.subjectAmyloiden
dc.subjectHTauP301Len
dc.subjectMitochondriaen
dc.titleAmyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in Alzheimer’s diseaseen
dc.typeinfo:eu-repo/semantics/articleen
dc.typeArtículo / Artikuluaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dspace.entity.typePublication
relation.isAuthorOfPublicationcc02d7db-8e88-40d1-81e0-834617b4849d
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscoverycc02d7db-8e88-40d1-81e0-834617b4849d

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