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Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease
Serrano-Pozo A, Li H, Li Z, Muñoz-Castro C, Jaisa-Aad M, Healey MA, Welikovitch LA, Jayakumar R et al.. Nature neuroscience, 2024-11-11
Topic: Genetics and APOE
Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer's disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis). The proportion of homeostatic, intermediate and reactive astrocytes changed only along the spatial axis, whereas two other subclusters changed along the temporal axis. One of these, a trophic factor-rich subcluster, declined along pathology stages, whereas the other increased in the late stage but returned to baseline levels in the end stage, suggesting an exhausted response with chronic exposure to neuropathology. Our study underscores the complex dynamics of astrocytic responses in AD.
Key findings
- Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum.
- We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis).
- The proportion of homeostatic, intermediate and reactive astrocytes changed only along the spatial axis, whereas two other subclusters changed along the temporal axis.
- One of these, a trophic factor-rich subcluster, declined along pathology stages, whereas the other increased in the late stage but returned to baseline levels in the end stage, suggesting an exhausted response with chronic exposure to neuropathology.
- Our study underscores the complex dynamics of astrocytic responses in AD.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty 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 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| 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 | 4 / 5 | 2024 — within 3 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 39528672) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Serrano-Pozo, A., Li, H., Li, Z., Muñoz-Castro, C., Jaisa-Aad, M., Healey, M. A., et al. (2024). Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease. Nature neuroscience. https://doi.org/10.1038/s41593-024-01791-4
Vancouver
Serrano-Pozo A, Li H, Li Z, Muñoz-Castro C, Jaisa-Aad M, Healey MA, et al. Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease. Nature neuroscience. 2024. doi:10.1038/s41593-024-01791-4. PMID: 39528672.
BibTeX
@article{serranopozo2024-39528672,
author = {Serrano-Pozo, A. and Li, H. and Li, Z. and Muñoz-Castro, C. and Jaisa-Aad, M. and Healey, M. A. and Welikovitch, L. A. and Jayakumar, R. and others},
title = {{Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease}},
journal = {Nature neuroscience},
year = {2024},
doi = {10.1038/s41593-024-01791-4},
pmid = {39528672},
url = {https://doi.org/10.1038/s41593-024-01791-4}
}
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