Early Alzheimer's disease pathology in human cortex involves transient cell states
Gazestani V, Kamath T, Nadaf NM, Dougalis A, Burris SJ, Rooney B, Junkkari A, Vanderburg C et al.. Cell, 2023-09-01
Topic: Inflammation, microglia and astrocytes
Cellular perturbations underlying Alzheimer's disease (AD) are primarily studied in human postmortem samples and model organisms. Here, we generated a single-nucleus atlas from a rare cohort of cortical biopsies from living individuals with varying degrees of AD pathology. We next performed a systematic cross-disease and cross-species integrative analysis to identify a set of cell states that are specific to early AD pathology. These changes-which we refer to as the early cortical amyloid response-were prominent in neurons, wherein we identified a transitional hyperactive state preceding the loss of excitatory neurons, which we confirmed by acute slice physiology on independent biopsy specimens. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathology increased. Finally, both oligodendrocytes and pyramidal neurons upregulated genes associated with β-amyloid production and processing during this early hyperactive phase. Our integrative analysis provides an organizing framework for targeting circuit dysfunction, neuroinflammation, and amyloid production early in AD pathogenesis.
Key findings
- Finally, both oligodendrocytes and pyramidal neurons upregulated genes associated with β-amyloid production and processing during this early hyperactive phase.
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Study details
- Evidence strengthModerate
How this study scored 43/100
Published in a peer-reviewed 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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| 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 | 3 / 5 | Rated “moderate” 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 | 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 37774681) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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APA 7th
Gazestani, V., Kamath, T., Nadaf, N. M., Dougalis, A., Burris, S. J., Rooney, B., et al. (2023). Early Alzheimer's disease pathology in human cortex involves transient cell states. Cell. https://doi.org/10.1016/j.cell.2023.08.005
Vancouver
Gazestani V, Kamath T, Nadaf NM, Dougalis A, Burris SJ, Rooney B, et al. Early Alzheimer's disease pathology in human cortex involves transient cell states. Cell. 2023. doi:10.1016/j.cell.2023.08.005. PMID: 37774681.
BibTeX
@article{gazestani2023-37774681,
author = {Gazestani, V. and Kamath, T. and Nadaf, N. M. and Dougalis, A. and Burris, S. J. and Rooney, B. and Junkkari, A. and Vanderburg, C. and others},
title = {{Early Alzheimer's disease pathology in human cortex involves transient cell states}},
journal = {Cell},
year = {2023},
doi = {10.1016/j.cell.2023.08.005},
pmid = {37774681},
url = {https://doi.org/10.1016/j.cell.2023.08.005}
}
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