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Brain Tissue-Derived Extracellular Vesicles in Alzheimer's Disease Display Altered Key Protein Levels Including Cell Type-Specific Markers.
Huang, Yiyao; Driedonks, Tom A P; Cheng, Lesley; Rajapaksha, Harinda; Routenberg, David A; Nagaraj, Rajini; Redding, Javier; Arab, Tanina; Powell, Bonita H; Pletniková, Olga; Troncoso, Juan C; Zheng, Lei; Hill, Andrew F; Mahairaki, Vasiliki; Witwer, Kenneth W.
Afiliación
  • Huang Y; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Driedonks TAP; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Cheng L; Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
  • Rajapaksha H; Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
  • Routenberg DA; Meso Scale Diagnostics, LLC, Rockville, MD, USA.
  • Nagaraj R; Meso Scale Diagnostics, LLC, Rockville, MD, USA.
  • Redding J; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Arab T; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Powell BH; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pletniková O; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Troncoso JC; Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
  • Zheng L; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hill AF; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mahairaki V; Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • Witwer KW; Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
J Alzheimers Dis ; 90(3): 1057-1072, 2022.
Article en En | MEDLINE | ID: mdl-36213994
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Vesículas Extracelulares Límite: Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Vesículas Extracelulares Límite: Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos