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Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology
Szebényi K, Wenger LMD, Sun Y, Dunn AWE, Limegrover CA, Gibbons GM, Conci E, Paulsen O et al.. Nature neuroscience, 2021-10-21
Topic: Brain proteins, microglia and lab models
Amyotrophic lateral sclerosis overlapping with frontotemporal dementia (ALS/FTD) is a fatal and currently untreatable disease characterized by rapid cognitive decline and paralysis. Elucidating initial cellular pathologies is central to therapeutic target development, but obtaining samples from presymptomatic patients is not feasible. Here, we report the development of a cerebral organoid slice model derived from human induced pluripotent stem cells (iPSCs) that recapitulates mature cortical architecture and displays early molecular pathology of C9ORF72 ALS/FTD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Szebényi, K., Wenger, L. M. D., Sun, Y., Dunn, A. W. E., Limegrover, C. A., Gibbons, G. M., et al. (2021). Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology. Nature neuroscience. https://doi.org/10.1038/s41593-021-00923-4
Vancouver
Szebényi K, Wenger LMD, Sun Y, Dunn AWE, Limegrover CA, Gibbons GM, et al. Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology. Nature neuroscience. 2021. doi:10.1038/s41593-021-00923-4. PMID: 34675437.
BibTeX
@article{szebenyi2021-34675437,
author = {Szebényi, K. and Wenger, L. M. D. and Sun, Y. and Dunn, A. W. E. and Limegrover, C. A. and Gibbons, G. M. and Conci, E. and Paulsen, O. and others},
title = {{Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology}},
journal = {Nature neuroscience},
year = {2021},
doi = {10.1038/s41593-021-00923-4},
pmid = {34675437},
url = {https://doi.org/10.1038/s41593-021-00923-4}
}
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.
Key findings
- Elucidating initial cellular pathologies is central to therapeutic target development, but obtaining samples from presymptomatic patients is not feasible.
- Here, we report the development of a cerebral organoid slice model derived from human induced pluripotent stem cells (iPSCs) that recapitulates mature cortical architecture and displays early molecular pathology of C9ORF72 ALS/FTD.
- Using a combination of single-cell RNA sequencing and biological assays, we reveal distinct transcriptional, proteostasis and DNA repair disturbances in astroglia and neurons.
- We show that astroglia display increased levels of the autophagy signaling protein P62 and that deep layer neurons accumulate dipeptide repeat protein poly(GA), DNA damage and undergo nuclear pyknosis that could be pharmacologically rescued by GSK2606414.
Why it matters
This study developed a human brain organoid slice model that shows early molecular pathology of C9ORF72 ALS/FTD and reveals early astrocyte and neuronal changes. It is a laboratory model of ALS/FTD, not Alzheimer's disease, and is early research that does not yet provide a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| Journal's citation record | 4 / 4 | Nature Neuroscience: journal h-index 593 (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 | 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 | Laboratory or animal study (title names “organoid”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 180 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 11.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 118 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author András Lakatos: h-index 21 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34675437) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41593-021-00923-4
- PubMed: 34675437
- Original source →
- Free full text: Nature Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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