Alzheimer's disease brain-derived extracellular vesicles reveal altered synapse-related proteome and induce cognitive impairment in mice

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBODART-SANTOS, Victor
dc.contributor.authorPINHEIRO, Lisandra S.
dc.contributor.authorSILVA-JUNIOR, Almir J. da
dc.contributor.authorFROZA, Rudimar L.
dc.contributor.authorAHRENS, Rosemary
dc.contributor.authorGONCALVES, Rafaella A.
dc.contributor.authorANDRADE, Mayara M.
dc.contributor.authorCHEN, Yan
dc.contributor.authorALCANTARA, Carolina de Lima
dc.contributor.authorGRINBERG, Lea T.
dc.contributor.authorLEITE, Renata E. P.
dc.contributor.authorFERREIRA, Sergio T.
dc.contributor.authorFRASER, Paul E.
dc.contributor.authorFELICE, Fernanda G. De
dc.date.accessioned2024-04-05T19:35:33Z
dc.date.available2024-04-05T19:35:33Z
dc.date.issued2023
dc.description.abstractINTRODUCTIONExtracellular vesicles (EVs) have been implicated in the spread of neuropathology in Alzheimer's disease (AD), but their involvement in behavioral outcomes linked to AD remains to be determined. METHODSEVs isolated from post mortem brain tissue from control, AD, or frontotemporal dementia (FTD) donors, as well as from APP/PS1 mice, were injected into the hippocampi of wild-type (WT) or a humanized Tau mouse model (hTau/mTauKO). Memory tests were carried out. Differentially expressed proteins in EVs were assessed by proteomics. RESULTSBoth AD-EVs and APP/PS1-EVs trigger memory impairment in WT mice. We further demonstrate that AD-EVs and FTD-EVs carry Tau protein, present altered protein composition associated with synapse regulation and transmission, and trigger memory impairment in hTau/mTauKO mice. DISCUSSIONResults demonstrate that AD-EVs and FTD-EVs have negative impacts on memory in mice and suggest that, in addition to spreading pathology, EVs may contribute to memory impairment in AD and FTD. HighlightsA beta was detected in EVs from post mortem AD brain tissue and APP/PS1 mice.Tau was enriched in EVs from post mortem AD, PSP and FTD brain tissue.AD-derived EVs and APP/PS1-EVs induce cognitive impairment in wild-type (WT) mice.AD- and FTD-derived EVs induce cognitive impairment in humanized Tau mice.Proteomics findings associate EVs with synapse dysregulation in tauopathies.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.indexWoS
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico
dc.description.sponsorshipNational Institute for Translational Neuroscience (INNT/Brazil)
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.description.sponsorshipNational Institute for Translational Neuroscience
dc.description.sponsorshipMinisterio da Saude/DECIT
dc.description.sponsorshipCanadian Institutes for Health Research [PJT-173487, 202104PJT-461851-NSB-CEDA-217167]
dc.description.sponsorshipInternational Society for Neurochemistry
dc.description.sponsorshipResearch Initiation Grant
dc.description.sponsorshipCanada Foundation for Innovation-John R. Evans Leaders Fund [43244]
dc.identifier.citationALZHEIMERS & DEMENTIA, v.19, n.12, p.5418-5436, 2023
dc.identifier.doi10.1002/alz.13134
dc.identifier.eissn1552-5279
dc.identifier.issn1552-5260
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/59026
dc.language.isoeng
dc.publisherWILEYeng
dc.relation.ispartofAlzheimers & Dementia
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright WILEYeng
dc.subjectAlzheimer's diseaseeng
dc.subjectbrain-derived EVseng
dc.subjectextracellular vesicleseng
dc.subjectproteomicseng
dc.subjecttauopathieseng
dc.subject.other5xfad mouse modeleng
dc.subject.otherterminal fragmentseng
dc.subject.otherneuronal exosomeseng
dc.subject.otherblood exosomeseng
dc.subject.otherin-vivoeng
dc.subject.othera-betaeng
dc.subject.othertaueng
dc.subject.otherproteinseng
dc.subject.othercelleng
dc.subject.otherprecursoreng
dc.subject.wosClinical Neurologyeng
dc.titleAlzheimer's disease brain-derived extracellular vesicles reveal altered synapse-related proteome and induce cognitive impairment in miceeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryisoca
hcfmusp.author.externalBODART-SANTOS, Victor:Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil; Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada
hcfmusp.author.externalPINHEIRO, Lisandra S.:Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil
hcfmusp.author.externalSILVA-JUNIOR, Almir J. da:Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, Brazil
hcfmusp.author.externalFROZA, Rudimar L.:Fiocruz MS, Oswaldo Cruz Fdn, Oswaldo Cruz Inst, Rio De Janeiro, Brazil
hcfmusp.author.externalAHRENS, Rosemary:Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada
hcfmusp.author.externalGONCALVES, Rafaella A.:Queens Univ, Ctr Neurosci Studies, Dept Biomed & Mol Sci, Kingston K7L 3N6, ON, Canada; Queens Univ, Dept Psychiat, Kingston, ON, Canada
hcfmusp.author.externalANDRADE, Mayara M.:Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil
hcfmusp.author.externalCHEN, Yan:Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada
hcfmusp.author.externalALCANTARA, Carolina de Lima:Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, Brazil
hcfmusp.author.externalFERREIRA, Sergio T.:Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil; Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, Brazil
hcfmusp.author.externalFRASER, Paul E.:Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada; Univ Toronto, Dept Med Biophys, Toronto, ON, Canada; Univ Toronto, Dept Med Biophys, Toronto, ON M5T 2S8, Canada
hcfmusp.author.externalFELICE, Fernanda G. De:Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil; Queens Univ, Ctr Neurosci Studies, Dept Biomed & Mol Sci, Kingston K7L 3N6, ON, Canada; Queens Univ, Dept Psychiat, Kingston, ON, Canada; DOR Inst Res & Educ, Rio De Janeiro, Brazil; Dept Psychiat, Kingston K7L 3N6, ON, Canada
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcLEA TENENHOLZ GRINBERG
hcfmusp.contributor.author-fmusphcRENATA ELAINE PARAIZO LEITE
hcfmusp.description.beginpage5418
hcfmusp.description.endpage5436
hcfmusp.description.issue12
hcfmusp.description.volume19
hcfmusp.origemWOS
hcfmusp.origem.dimensionspub.1158190887
hcfmusp.origem.pubmed37204850
hcfmusp.origem.scopus2-s2.0-85159667042
hcfmusp.origem.wosWOS:000991467500001
hcfmusp.publisher.cityHOBOKENeng
hcfmusp.publisher.countryUSAeng
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