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Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain
You Y, Muraoka S, Jedrychowski MP, Hu J, McQuade AK, Young-Pearse T, Aslebagh R, Shaffer SA et al.. Journal of extracellular vesicles, 2022-01-01
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
Why it matters
This study identified cell type-specific extracellular vesicle protein markers and found that a protein module enriched in astrocyte-specific markers was most significantly associated with Alzheimer's disease pathology and cognitive impairment. The hub protein integrin-β1 was elevated in astrocyte-specific vesicles and associated with brain β-amyloid and tau load, suggesting a role in disease progression rather than a treatment.
Study details
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of extracellular vesicles) |
| Journal's citation record | 2 / 4 | Journal of Extracellular Vesicles: journal h-index 171 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 161 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 4 / 6 | Cited 9.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 109 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Tsuneya Ikezu: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35029059) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/jev2.12183
- PubMed: 35029059
- Original source →
- Free full text: Journal of Extracellular Vesicles →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
You, Y., Muraoka, S., Jedrychowski, M. P., Hu, J., McQuade, A. K., Young-Pearse, T., et al. (2022). Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain. Journal of extracellular vesicles. https://doi.org/10.1002/jev2.12183
Vancouver
You Y, Muraoka S, Jedrychowski MP, Hu J, McQuade AK, Young-Pearse T, et al. Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain. Journal of extracellular vesicles. 2022. doi:10.1002/jev2.12183. PMID: 35029059.
BibTeX
@article{you2022-35029059,
author = {You, Y. and Muraoka, S. and Jedrychowski, M. P. and Hu, J. and McQuade, A. K. and Young-Pearse, T. and Aslebagh, R. and Shaffer, S. A. and others},
title = {{Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain}},
journal = {Journal of extracellular vesicles},
year = {2022},
doi = {10.1002/jev2.12183},
pmid = {35029059},
url = {https://doi.org/10.1002/jev2.12183}
}
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