Home › Research › Disease mechanisms
A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late‐stage neuronal Tau pathology
Angelika Dannert. Alzheimer s & Dementia, 2025-12-01
Topic: Brain proteins, microglia and lab models
We found that induction of adult human brain-like 4R Tau isoform expression enables endogenous formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations. Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures. Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation. Finally, we found proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate a human Tau PET tracer. Collectively, our model enables novel investigations on endogenous mechanisms of human Tauopathy formation, suggesting a central role of 4R Tau isoform expression for pathogenesis in human neurons. Moreover, it may also serve as a platform supporting urgently needed development of disease-modifying drugs.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dannert, A. (2025). A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late‐stage neuronal Tau pathology. Alzheimer s & Dementia. https://doi.org/10.1002/alz70855_100354
Vancouver
Dannert A. A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late‐stage neuronal Tau pathology. Alzheimer s & Dementia. 2025. doi:10.1002/alz70855_100354. PMID: 41452866.
BibTeX
@article{dannert2025-41452866,
author = {Dannert, Angelika},
title = {{A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late‐stage neuronal Tau pathology}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70855_100354},
pmid = {41452866},
url = {https://doi.org/10.1002/alz70855_100354}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- We found that induction of adult human brain-like 4R Tau isoform expression enables endogenous formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations.
- Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures.
- Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation.
- Finally, we found proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate a human Tau PET tracer.
- Collectively, our model enables novel investigations on endogenous mechanisms of human Tauopathy formation, suggesting a central role of 4R Tau isoform expression for pathogenesis in human neurons.
Why it matters
iPSC-derived neurons engineered to express adult brain-like 4R tau with synergistic tau mutations developed seeding-competent, hyperphosphorylated, fibrillar tau in tangle-like structures, and the model was used to test chemical modulators and a human tau PET tracer. This is a laboratory model for research and drug development, not a treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 33/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | Laboratory or animal study (title names “ipsc”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Angelika Dannert: h-index 6 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41452866) |
| Free to read | 2 / 2 | Free to read |
| Total | 33 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70855_100354
- PubMed: 41452866
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Disease mechanisms
Also tagged “phosphorylated”
732 studies in the library carry the topic tag “phosphorylated”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 732 tagged studies.