Loading...
Thumbnail Image
Publication

Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain

You, Yang
Muraoka, Satoshi
Jedrychowski, Mark P
Hu, Jianqiao
McQuade, Amanda K
Young-Pearse, Tracy
Aslebagh, Roshanak
Shaffer, Scott A
Gygi, Steven P
Blurton-Jones, Mathew
... show 2 more
Embargo Expiration Date
Abstract

In neurodegenerative diseases, extracellular vesicles (EVs) transfer pathogenic molecules and are consequently involved in disease progression. We have investigated the proteomic profiles of EVs that were isolated from four different human-induced pluripotent stem cell-derived neural cell types (excitatory neurons, astrocytes, microglia-like cells, and oligodendrocyte-like cells). Novel cell type-specific EV protein markers were then identified for the excitatory neurons (ATP1A3, NCAM1), astrocytes (LRP1, ITGA6), microglia-like cells (ITGAM, LCP1), and oligodendrocyte-like cells (LAMP2, FTH1), as well as 16 pan-EV marker candidates, including integrins and annexins. To further demonstrate how cell-type-specific EVs may be involved in Alzheimer's disease (AD), we performed protein co-expression network analysis and conducted cell type assessments for the proteomes of brain-derived EVs from the control, mild cognitive impairment, and AD cases. A protein module enriched in astrocyte-specific EV markers was most significantly associated with the AD pathology and cognitive impairment, suggesting an important role in AD progression. The hub protein from this module, integrin-β1 (ITGB1), was found to be significantly elevated in astrocyte-specific EVs enriched from the total brain-derived AD EVs and associated with the brain β-amyloid and tau load in independent cohorts. Thus, our study provides a featured framework and rich resource for the future analyses of EV functions in neurodegenerative diseases in a cell type-specific manner.

Source

You Y, Muraoka S, Jedrychowski MP, Hu J, McQuade AK, Young-Pearse T, Aslebagh R, Shaffer SA, Gygi SP, Blurton-Jones M, Poon WW, Ikezu T. Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain. J Extracell Vesicles. 2022 Jan;11(1):e12183. doi: 10.1002/jev2.12183. PMID: 35029059; PMCID: PMC8758831.

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.1002/jev2.12183
PubMed ID
35029059
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivsLicense, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular VesiclesAttribution-NonCommercial-NoDerivatives 4.0 International