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Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology
Mathys H, Peng Z, Boix CA, Victor MB, Leary N, Babu S, Abdelhady G, Jiang X et al.. Cell, 2023-09-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology.
Key findings
- To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment.
- Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology.
- Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.
Why it matters
In prefrontal cortex tissue donated after death by 427 people (2.3 million cells), certain somatostatin inhibitory neurons were depleted in Alzheimer's disease. Two groups of inhibitory neurons were more abundant in people who kept high cognitive function late in life. The study also found increases in the cohesin complex and DNA damage response factors in excitatory neurons and oligodendrocytes. These are associations measured once, after death: they do not show that these cells protect memory or that any treatment would help.
Study details
- Participants427
- Evidence strengthLow
How this study scored 65/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (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 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 427 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 491 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 98.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 6 / 6 | Cited 71.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 23 other studies in this library |
| Still being cited | 4 / 4 | Cited 467 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Li‐Huei Tsai: h-index 131 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Massachusetts Institute of Technology: institution h-index 2,557 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37774677) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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APA 7th
Mathys, H., Peng, Z., Boix, C. A., Victor, M. B., Leary, N., Babu, S., et al. (2023). Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology. Cell. https://doi.org/10.1016/j.cell.2023.08.039
Vancouver
Mathys H, Peng Z, Boix CA, Victor MB, Leary N, Babu S, et al. Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology. Cell. 2023. doi:10.1016/j.cell.2023.08.039. PMID: 37774677.
BibTeX
@article{mathys2023-37774677,
author = {Mathys, H. and Peng, Z. and Boix, C. A. and Victor, M. B. and Leary, N. and Babu, S. and Abdelhady, G. and Jiang, X. and others},
title = {{Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology}},
journal = {Cell},
year = {2023},
doi = {10.1016/j.cell.2023.08.039},
pmid = {37774677},
url = {https://doi.org/10.1016/j.cell.2023.08.039}
}
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