Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer's disease
Gen Lin, Sarah E Chancellor, Taekyung Kwon, Maya E Woodbury, Astrid Doering, Aicha Abdourahman, Rachel E Bennett, Fan Liao et al.. Cell reports, 2025-05-29
Topic: Disease mechanisms in lab and animal studies
Neuronal loss is the ultimate driver of neural system dysfunction in Alzheimer's disease (AD). We used single-nucleus RNA sequencing and neuropathological phenotyping to elucidate mechanisms of neurodegeneration in AD by identifying vulnerable neuronal populations and probing for their differentially expressed genes. Evidenced by transcriptomic analyses and quantitative tau immunoassays of human AD and non-AD brain tissue, we identified a neuronal population especially vulnerable to tau pathology. Multiplexed immunohistochemistry and in situ hybridization (CBLN2 and LINC00507) validated the presence of the tau-vulnerable neuronal population and revealed a propensity of this population to bear tau pathology. Differentially expressed genes associated with phospho-tau pathology in these neurons revealed genes involved in apoptosis, cell-component dissociation (e.g., autophagosome maturation and actin filament depolymerization), and regulation of vesicle-mediated transport.
Key findings
- Multiplexed immunohistochemistry and in situ hybridization (CBLN2 and LINC00507) validated the presence of the tau-vulnerable neuronal population and revealed a propensity of this population to bear tau pathology.
- Differentially expressed genes associated with phospho-tau pathology in these neurons revealed genes involved in apoptosis, cell-component dissociation (e.g., autophagosome maturation and actin filament depolymerization), and regulation of vesicle-mediated transport.
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Study details
- Evidence strengthLow
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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 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 reports) |
| 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 | 2025 — 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 40448997) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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APA 7th
Lin, G., Chancellor, S. E., Kwon, T., Woodbury, M. E., Doering, A., Abdourahman, A., et al. (2025). Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer's disease. Cell reports. https://doi.org/10.1016/j.celrep.2025.115758
Vancouver
Lin G, Chancellor SE, Kwon T, Woodbury ME, Doering A, Abdourahman A, et al. Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer's disease. Cell reports. 2025. doi:10.1016/j.celrep.2025.115758. PMID: 40448997.
BibTeX
@article{lin2025-40448997,
author = {Lin, Gen and Chancellor, Sarah E and Kwon, Taekyung and Woodbury, Maya E and Doering, Astrid and Abdourahman, Aicha and Bennett, Rachel E and Liao, Fan and others},
title = {{Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer's disease}},
journal = {Cell reports},
year = {2025},
doi = {10.1016/j.celrep.2025.115758},
pmid = {40448997},
url = {https://doi.org/10.1016/j.celrep.2025.115758}
}