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Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease
Apodaca LA, Baddour AAD, Garcia C, Alikhani L, Giedzinski E, Ru N, Agrawal A, Acharya MM et al.. Alzheimer's research & therapy, 2021-03-06
Topic: Brain proteins, microglia and lab models
Background Regenerative therapies to mitigate Alzheimer's disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EVs) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions. Methods Using the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EVs on the neurocognitive and neuropathologic hallmarks in the AD brain. Two- or 6-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EVs, respectively. Results RO treatment using hNSC-derived EVs restored fear extinction memory consolidation and reduced anxiety-related behaviors 4-6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function. Conclusions Collectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EVs for remediation of behavioral and molecular AD neuropathologies.
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APA 7th
Apodaca, L. A., Baddour, A. A. D., Garcia, C., Alikhani, L., Giedzinski, E., Ru, N., et al. (2021). Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-021-00791-x
Vancouver
Apodaca LA, Baddour AAD, Garcia C, Alikhani L, Giedzinski E, Ru N, et al. Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease. Alzheimer's research & therapy. 2021. doi:10.1186/s13195-021-00791-x. PMID: 33676561.
BibTeX
@article{apodaca2021-33676561,
author = {Apodaca, L. A. and Baddour, A. A. D. and Garcia, C. and Alikhani, L. and Giedzinski, E. and Ru, N. and Agrawal, A. and Acharya, M. M. and others},
title = {{Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease}},
journal = {Alzheimer's research \& therapy},
year = {2021},
doi = {10.1186/s13195-021-00791-x},
pmid = {33676561},
url = {https://doi.org/10.1186/s13195-021-00791-x}
}
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Key findings
- Results RO treatment using hNSC-derived EVs restored fear extinction memory consolidation and reduced anxiety-related behaviors 4-6 weeks post-injection.
- EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups.
- These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice.
- MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function.
Study details
- Evidence strengthLow
How this study scored 43/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2021 — 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33676561) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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