Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease
Emily Miyoshi, Samuel Morabito, Caden M Henningfield, Sudeshna Das, Negin Rahimzadeh, Sepideh Kiani Shabestari, Neethu Michael, Nora Emerson et al.. Nature genetics, 2024-11-22
Topic: Genetics and APOE
The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with its molecular etiology still unclear. Here we present a spatial transcriptomic (ST) and single-nucleus transcriptomic survey of late-onset sporadic AD and AD in Down syndrome (DSAD). Studying DSAD provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD. We identified transcriptomic changes that may underlie cortical layer-preferential pathology accumulation. Spatial co-expression network analyses revealed transient and regionally restricted disease processes, including a glial inflammatory program dysregulated in upper cortical layers and implicated in AD genetic risk and amyloid-associated processes. Cell-cell communication analysis further contextualized this gene program in dysregulated signaling networks. Finally, we generated ST data from an amyloid AD mouse model to identify cross-species amyloid-proximal transcriptomic changes with conformational context.
Key findings
- Spatial co-expression network analyses revealed transient and regionally restricted disease processes, including a glial inflammatory program dysregulated in upper cortical layers and implicated in AD genetic risk and amyloid-associated processes.
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Study details
- Evidence strengthLow
How this study scored 46/100
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, multi-centre collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| 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 39578645) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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APA 7th
Miyoshi, E., Morabito, S., Henningfield, C. M., Das, S., Rahimzadeh, N., Shabestari, S. K., et al. (2024). Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease. Nature genetics. https://doi.org/10.1038/s41588-024-01961-x
Vancouver
Miyoshi E, Morabito S, Henningfield CM, Das S, Rahimzadeh N, Shabestari SK, et al. Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease. Nature genetics. 2024. doi:10.1038/s41588-024-01961-x. PMID: 39578645.
BibTeX
@article{miyoshi2024-39578645,
author = {Miyoshi, Emily and Morabito, Samuel and Henningfield, Caden M and Das, Sudeshna and Rahimzadeh, Negin and Shabestari, Sepideh Kiani and Michael, Neethu and Emerson, Nora and others},
title = {{Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease}},
journal = {Nature genetics},
year = {2024},
doi = {10.1038/s41588-024-01961-x},
pmid = {39578645},
url = {https://doi.org/10.1038/s41588-024-01961-x}
}