Brain Tissue-Derived Extracellular Vesicles in Alzheimer's Disease Display Altered Key Protein Levels Including Cell Type-Specific Markers.

Humans Alzheimer Disease / pathology Proteome / metabolism Brain / pathology Extracellular Vesicles / metabolism Neurons / metabolism
Alzheimer’s disease brain cell of origin markers central nervous system ectosomes exosomes extracellular vesicles microvesicles proteomics

Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2022
Historique:
pubmed: 11 10 2022
medline: 1 12 2022
entrez: 10 10 2022
Statut: ppublish

Résumé

Brain tissue-derived extracellular vesicles (bdEVs) play neurodegenerative and protective roles, including in Alzheimer's disease (AD). Extracellular vesicles (EVs) may also leave the brain to betray the state of the CNS in the periphery. Only a few studies have profiled the proteome of bdEVs and source brain tissue. Additionally, studies focusing on bdEV cell type-specific surface markers are rare. We aimed to reveal the pathological mechanisms inside the brain by profiling the tissue and bdEV proteomes in AD patients. In addition, to indicate targets for capturing and molecular profiling of bdEVs in the periphery, CNS cell-specific markers were profiled on the intact bdEV surface. bdEVs were separated and followed by EV counting and sizing. Brain tissue and bdEVs from age-matched AD patients and controls were then proteomically profiled. Total tau (t-tau), phosphorylated tau (p-tau), and antioxidant peroxiredoxins (PRDX) 1 and 6 were measured by immunoassay in an independent bdEV separation. Neuron, microglia, astrocyte, and endothelia markers were detected on intact EVs by multiplexed ELISA. Overall, concentration of recovered bdEVs was not affected by AD. Proteome differences between AD and control were more pronounced for bdEVs than for brain tissue. Levels of t-tau, p-tau, PRDX1, and PRDX6 were significantly elevated in AD bdEVs compared with controls. Release of certain cell-specific bdEV markers was increased in AD. Several bdEV proteins are involved in AD mechanisms and may be used for disease monitoring. The identified CNS cell markers may be useful tools for peripheral bdEV capture.

Sections du résumé

BACKGROUND
Brain tissue-derived extracellular vesicles (bdEVs) play neurodegenerative and protective roles, including in Alzheimer's disease (AD). Extracellular vesicles (EVs) may also leave the brain to betray the state of the CNS in the periphery. Only a few studies have profiled the proteome of bdEVs and source brain tissue. Additionally, studies focusing on bdEV cell type-specific surface markers are rare.
OBJECTIVE
We aimed to reveal the pathological mechanisms inside the brain by profiling the tissue and bdEV proteomes in AD patients. In addition, to indicate targets for capturing and molecular profiling of bdEVs in the periphery, CNS cell-specific markers were profiled on the intact bdEV surface.
METHODS
bdEVs were separated and followed by EV counting and sizing. Brain tissue and bdEVs from age-matched AD patients and controls were then proteomically profiled. Total tau (t-tau), phosphorylated tau (p-tau), and antioxidant peroxiredoxins (PRDX) 1 and 6 were measured by immunoassay in an independent bdEV separation. Neuron, microglia, astrocyte, and endothelia markers were detected on intact EVs by multiplexed ELISA.
RESULTS
Overall, concentration of recovered bdEVs was not affected by AD. Proteome differences between AD and control were more pronounced for bdEVs than for brain tissue. Levels of t-tau, p-tau, PRDX1, and PRDX6 were significantly elevated in AD bdEVs compared with controls. Release of certain cell-specific bdEV markers was increased in AD.
CONCLUSION
Several bdEV proteins are involved in AD mechanisms and may be used for disease monitoring. The identified CNS cell markers may be useful tools for peripheral bdEV capture.

Identifiants

DOI: 10.3233/JAD-220322 PMID: 36213994 PMC: PMC9741741
pubmed: 36213994
pii: JAD220322
doi: 10.3233/JAD-220322
pmc: PMC9741741
doi:

Substances chimiques

Proteome 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1057-1072

Subventions

Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047807
Pays : United States
Organisme : NIMH NIH HHS
ID : R33 MH118164
Pays : United States
Organisme : NCI NIH HHS
ID : UG3 CA241694
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI144997
Pays : United States
Organisme : NCI NIH HHS
ID : UH3 CA241694
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG033655
Pays : United States
Organisme : NIMH NIH HHS
ID : UH2 MH118167
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH118164
Pays : United States

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Auteurs

Yiyao Huang (Y)

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Tom A P Driedonks (TAP)

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Lesley Cheng (L)

Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.

Harinda Rajapaksha (H)

Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.

David A Routenberg (DA)

Meso Scale Diagnostics, LLC, Rockville, MD, USA.

Rajini Nagaraj (R)

Meso Scale Diagnostics, LLC, Rockville, MD, USA.

Javier Redding (J)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Tanina Arab (T)

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Bonita H Powell (BH)

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Olga Pletniková (O)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Juan C Troncoso (JC)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Lei Zheng (L)

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Andrew F Hill (AF)

Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Institute of Health and Sport, Victoria University, Melbourne, VIC, Australia.

Vasiliki Mahairaki (V)

Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Kenneth W Witwer (KW)

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Brain Tissue-Derived Extracellular Vesicles in...
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questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Brain Tissue-Derived Extracellular Vesicles in...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Vésicules extracellulaires › Brain Tissue-Derived Extracellular Vesicles in...
questionsmedicales.fr › Cellules › Neurones › Brain Tissue-Derived Extracellular Vesicles in...