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Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities
Filippa Lo Cascio, S.J. Park, Urmi Sengupta, Nicha Puangmalai, Nemil N. Bhatt, Nikita Shchankin, Cynthia Jerez, Naomi Moreno et al.. Communications Biology, 2025-01-14
Topic: Brain proteins, microglia and lab models
Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs. Here, we investigate the structural and functional differences of amplified brain-derived tau oligomers (aBDTOs) from AD, DLB, and PSP. Our results indicate that the aBDTOs possess different structural and morphological features that impact neuronal function, gene regulation, and ultimately disease progression. The distinct tau oligomeric polymorphs may thus contribute to the development of clinical phenotypes and shape the progression of diseases. Our results can provide insight into developing personalized therapy to target a specific neurotoxic tau polymorph. Different aggregation characteristics and stability profiles of tau oligomeric polymorphs highlight the importance of studying the tau polymorphs to shed light on the functional differences and neuropathological heterogeneity in tauopathies.
Key findings
- Our results indicate that the aBDTOs possess different structural and morphological features that impact neuronal function, gene regulation, and ultimately disease progression.
- Our results can provide insight into developing personalized therapy to target a specific neurotoxic tau polymorph.
Why it matters
Tau oligomers amplified from the brains of people with Alzheimer's disease, dementia with Lewy bodies, and progressive supranuclear palsy differed in structure and stability and affected neuronal function differently. This suggests that therapies might one day be tailored to specific tau forms, but the work is laboratory-based and no treatment is established.
Study details
- Evidence strengthLow
How this study scored 45/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Communications Biology) |
| Journal's citation record | 1 / 4 | Communications Biology: journal h-index 142 (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 | 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 | 3 / 7 | Cited 35 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 19.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rakez Kayed: h-index 76 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The Ohio State University: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39809992) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s42003-025-07499-w
- PubMed: 39809992
- Original source →
- Free full text: Communications Biology →
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
Cascio, F. L., Park, S., Sengupta, U., Puangmalai, N., Bhatt, N. N., Shchankin, N., et al. (2025). Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities. Communications Biology. https://doi.org/10.1038/s42003-025-07499-w
Vancouver
Cascio FL, Park S, Sengupta U, Puangmalai N, Bhatt NN, Shchankin N, et al. Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities. Communications Biology. 2025. doi:10.1038/s42003-025-07499-w. PMID: 39809992.
BibTeX
@article{cascio2025-39809992,
author = {Cascio, Filippa Lo and Park, S.J. and Sengupta, Urmi and Puangmalai, Nicha and Bhatt, Nemil N. and Shchankin, Nikita and Jerez, Cynthia and Moreno, Naomi and others},
title = {{Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities}},
journal = {Communications Biology},
year = {2025},
doi = {10.1038/s42003-025-07499-w},
pmid = {39809992},
url = {https://doi.org/10.1038/s42003-025-07499-w}
}
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