Home › Research › Brain tissue and pathology
Single-cell multiregion dissection of Alzheimer's disease
Mathys H, Boix CA, Akay LA, Xia Z, Davila-Velderrain J, Ng AP, Jiang X, Abdelhady G et al.. Nature, 2024-07-24
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood 1-3 . Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses.
Key findings
- Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease.
- We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses.
- We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer's disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons.
- We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer's disease and to annotate transcriptomic differences associated with diverse pathological variables.
Why it matters
This study built a single-cell atlas of six brain regions from 283 post-mortem samples, identifying 76 cell types and vulnerable populations of excitatory neurons. It is a descriptive map of brain tissue and does not test a treatment, cure, or prevention for Alzheimer's disease.
Study details
- Participants48
- Evidence strengthLow
How this study scored 69/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 48 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 312 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 78.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 36.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 4 / 4 | Cited 310 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Manolis Kellis: h-index 141 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39048816) |
| Free to read | 2 / 2 | Free to read |
| Total | 69 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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
Mathys, H., Boix, C. A., Akay, L. A., Xia, Z., Davila-Velderrain, J., Ng, A. P., et al. (2024). Single-cell multiregion dissection of Alzheimer's disease. Nature. https://doi.org/10.1038/s41586-024-07606-7
Vancouver
Mathys H, Boix CA, Akay LA, Xia Z, Davila-Velderrain J, Ng AP, et al. Single-cell multiregion dissection of Alzheimer's disease. Nature. 2024. doi:10.1038/s41586-024-07606-7. PMID: 39048816.
BibTeX
@article{mathys2024-39048816,
author = {Mathys, H. and Boix, C. A. and Akay, L. A. and Xia, Z. and Davila-Velderrain, J. and Ng, A. P. and Jiang, X. and Abdelhady, G. and others},
title = {{Single-cell multiregion dissection of Alzheimer's disease}},
journal = {Nature},
year = {2024},
doi = {10.1038/s41586-024-07606-7},
pmid = {39048816},
url = {https://doi.org/10.1038/s41586-024-07606-7}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 18.
Later studies that cite this one
7 studies in the alzhub library list this one in their references.
Related studies in Brain tissue and pathology
Also in Brain tissue and pathology
124 studies in the library are filed under Brain tissue and pathology with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Brain tissue and pathology hub.