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Cellular communities reveal trajectories of brain ageing and Alzheimer's disease
Green GS, Fujita M, Yang HS, Taga M, Cain A, McCabe C, Comandante-Lou N, White CC et al.. Nature, 2024-08-28
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) has recently been associated with diverse cell states 1-11 , yet when and how these states affect the onset of AD remains unclear. Here we used a data-driven approach to reconstruct the dynamics of the brain's cellular environment and identified a trajectory leading to AD that is distinct from other ageing-related effects. First, we built a comprehensive cell atlas of the aged prefrontal cortex from 1.65 million single-nucleus RNA-sequencing profiles sampled from 437 older individuals, and identified specific glial and neuronal subpopulations associated with AD-related traits.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Green, G. S., Fujita, M., Yang, H. S., Taga, M., Cain, A., McCabe, C., et al. (2024). Cellular communities reveal trajectories of brain ageing and Alzheimer's disease. Nature. https://doi.org/10.1038/s41586-024-07871-6
Vancouver
Green GS, Fujita M, Yang HS, Taga M, Cain A, McCabe C, et al. Cellular communities reveal trajectories of brain ageing and Alzheimer's disease. Nature. 2024. doi:10.1038/s41586-024-07871-6. PMID: 39198642.
BibTeX
@article{green2024-39198642,
author = {Green, G. S. and Fujita, M. and Yang, H. S. and Taga, M. and Cain, A. and McCabe, C. and Comandante-Lou, N. and White, C. C. and others},
title = {{Cellular communities reveal trajectories of brain ageing and Alzheimer's disease}},
journal = {Nature},
year = {2024},
doi = {10.1038/s41586-024-07871-6},
pmid = {39198642},
url = {https://doi.org/10.1038/s41586-024-07871-6}
}
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Key findings
- Here we used a data-driven approach to reconstruct the dynamics of the brain's cellular environment and identified a trajectory leading to AD that is distinct from other ageing-related effects.
- First, we built a comprehensive cell atlas of the aged prefrontal cortex from 1.65 million single-nucleus RNA-sequencing profiles sampled from 437 older individuals, and identified specific glial and neuronal subpopulations associated with AD-related traits.
- Causal modelling then prioritized two distinct lipid-associated microglial subpopulations-one drives amyloid-β proteinopathy while the other mediates the effect of amyloid-β on tau proteinopathy-as well as an astrocyte subpopulation that mediates the effect of tau on cognitive decline.
- To model the dynamics of cellular environments, we devised the BEYOND methodology, which identified two distinct trajectories of brain ageing, each defined by coordinated progressive changes in certain cellular communities that lead to (1) AD dementia or (2) alternative brain ageing.
Why it matters
Using 1.65 million single-cell gene-activity profiles from the prefrontal cortex of 437 older people, this study mapped how brain cell populations shift with age and found two paths: one leading to Alzheimer's dementia and one to "alternative brain ageing." Its causal modelling pointed to two lipid-associated microglia groups — one linked to amyloid build-up, the other to amyloid's effect on tau — and an astrocyte group linked to tau's effect on cognitive decline. These are statistical links in brain tissue, not a tested treatment, test or cure.
Study details
- Evidence strengthLow
How this study scored 60/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 | 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 195 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 48.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 22.8× 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 | 3 / 4 | Cited 194 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Philip L. De Jager: h-index 143 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39198642) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41586-024-07871-6
- PubMed: 39198642
- Original source →
- Free full text: Europe PMC (PubMed Central) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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