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Understanding Tau pathology: Insights from animal models
Han Zhang, Ming-Tian Pan, Yu-Xuan Li, Xiao-Jiang Li, Xiang-Yu Guo, Da-Jian He. Zoological research, 2025-09-18
Topic: Disease mechanisms in lab and animal studies
Tauopathies represent a class of neurodegenerative diseases (NDs), including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Pick's disease (PiD), and corticobasal degeneration (CBD), defined by intracellular accumulation of misfolded and hyperphosphorylated tau protein. The pathogenic cascade involves hyperphosphorylation, conformational changes, and aggregation into neurofibrillary tangles (NFTs), which are spatially and functionally linked to neuronal dysfunction, synaptic loss, and progressive cognitive and motor decline. To elucidate tau-mediated mechanisms, diverse transgenic rodent models expressing wild-type or mutant forms of human TAU have been generated. Although these models have advanced understanding of tau aggregation and propagation, tau-targeting therapies have failed to produce clinical benefits, raising concerns about the precise mechanism underlying tauopathies and the fidelity of animal models in evaluating therapeutic targets. This review systematically examines the neuropathological and behavioral phenotypes across established rodent and non-human primate (NHP) tauopathy models, highlighting mechanistic insights into tau-driven pathology. The advantages, limitations, and translational barriers of each model are critically evaluated to inform the development of more predictive preclinical platforms for therapeutic discovery.
Key findings
- The pathogenic cascade involves hyperphosphorylation, conformational changes, and aggregation into neurofibrillary tangles (NFTs), which are spatially and functionally linked to neuronal dysfunction, synaptic loss, and progressive cognitive and motor decline.
- To elucidate tau-mediated mechanisms, diverse transgenic rodent models expressing wild-type or mutant forms of human TAU have been generated.
- Although these models have advanced understanding of tau aggregation and propagation, tau-targeting therapies have failed to produce clinical benefits, raising concerns about the precise mechanism underlying tauopathies and the fidelity of animal models in evaluating therapeutic targets.
- This review systematically examines the neuropathological and behavioral phenotypes across established rodent and non-human primate (NHP) tauopathy models, highlighting mechanistic insights into tau-driven pathology.
- The advantages, limitations, and translational barriers of each model are critically evaluated to inform the development of more predictive preclinical platforms for therapeutic discovery.
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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 (Zoological research) |
| 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 41017406) |
| 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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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Zhang, H., Pan, M.-T., Li, Y.-X., Li, X.-J., Guo, X.-Y., & He, D.-J. (2025). Understanding Tau pathology: Insights from animal models. Zoological research. https://doi.org/10.24272/j.issn.2095-8137.2025.077
Vancouver
Zhang H, Pan M.-T, Li Y.-X, Li X.-J, Guo X.-Y, He D.-J. Understanding Tau pathology: Insights from animal models. Zoological research. 2025. doi:10.24272/j.issn.2095-8137.2025.077. PMID: 41017406.
BibTeX
@article{zhang2025-41017406,
author = {Zhang, Han and Pan, Ming-Tian and Li, Yu-Xuan and Li, Xiao-Jiang and Guo, Xiang-Yu and He, Da-Jian},
title = {{Understanding Tau pathology: Insights from animal models}},
journal = {Zoological research},
year = {2025},
doi = {10.24272/j.issn.2095-8137.2025.077},
pmid = {41017406},
url = {https://doi.org/10.24272/j.issn.2095-8137.2025.077}
}