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

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Citações na Scopus
1
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
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Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY
Autores
BODART-SANTOS, Victor
PINHEIRO, Lisandra S.
SILVA-JUNIOR, Almir J. da
FROZA, Rudimar L.
AHRENS, Rosemary
GONCALVES, Rafaella A.
ANDRADE, Mayara M.
CHEN, Yan
ALCANTARA, Carolina de Lima
Citação
ALZHEIMERS & DEMENTIA, v.19, n.12, p.5418-5436, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
INTRODUCTIONExtracellular 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.
Palavras-chave
Alzheimer's disease, brain-derived EVs, extracellular vesicles, proteomics, tauopathies
URI
https://observatorio.fm.usp.br/handle/OPI/59026
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Artigos e Materiais de Revistas Científicas - FM/MPT