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Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences
Muhammad Ali, Pierre Garcia, Laetitia P. Lunkes, Alessia Sciortino, Mélanie H. Thomas, Tony Heurtaux, Kamil Grzyb, Rashi Halder et al.. Acta Neuropathologica Communications, 2025-05-07
Topic: Brain proteins, microglia and lab models
We identified several significant sex-specific and sex-dimorphic differentially expressed genes in neurons, microglia, astrocytes and oligodendrocytes, including both cross-sectional changes and alterations from 7 months to 17 months of age. Key pathways affected in a sex-dependent manner across age included neurotransmitter signaling, RNA processing and splicing, stress response pathways, and protein degradation pathways. In addition, network analysis revealed the AD-associated genes Clu, Mbp, Fos and Junb as relevant regulatory hubs. Analysis of age-dependent changes highlighted genes and pathways associated with inflammatory response (Malat1, Cx3cr1), protein homeostasis (Cst3), and myelin maintenance (Plp1, Cldn11, Mal) that showed consistent sex-dependent changes as the THY-Tau22 mice aged. Multiple genes with established implications in AD, including the long non-coding RNA gene Malat1, displayed concordant sex-specific changes in mouse models and human AD. This study provides a comprehensive single-cell transcriptomic characterization of sex-linked and age-dependent changes in the THY-Tau22 tauopathy model, revealing new insights into the interplay between age-dependent AD-like pathologies and sex. The identified sex-specific changes and their conservation across models and human AD highlight molecular targets for further preclinical investigation of sex-specific therapeutic strategies in AD.
Key findings
- We identified several significant sex-specific and sex-dimorphic differentially expressed genes in neurons, microglia, astrocytes and oligodendrocytes, including both cross-sectional changes and alterations from 7 months to 17 months of age.
- Key pathways affected in a sex-dependent manner across age included neurotransmitter signaling, RNA processing and splicing, stress response pathways, and protein degradation pathways.
- In addition, network analysis revealed the AD-associated genes Clu, Mbp, Fos and Junb as relevant regulatory hubs.
- Analysis of age-dependent changes highlighted genes and pathways associated with inflammatory response (Malat1, Cx3cr1), protein homeostasis (Cst3), and myelin maintenance (Plp1, Cldn11, Mal) that showed consistent sex-dependent changes as the THY-Tau22 mice aged.
- Multiple genes with established implications in AD, including the long non-coding RNA gene Malat1, displayed concordant sex-specific changes in mouse models and human AD.
Why it matters
In the THY-Tau22 mouse model of tauopathy, single-cell transcriptomics found sex-specific and age-dependent gene changes in neurons, microglia, astrocytes, and oligodendrocytes, with some changes matching those seen in human Alzheimer's disease. The authors highlight molecular targets for further preclinical investigation of sex-specific therapies, based on animal work.
Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta Neuropathologica Communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.2× 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 | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Enrico Glaab: h-index 43 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40336141) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-025-02013-z
- PubMed: 40336141
- Original source →
- Free full text: Acta Neuropathologica Communications →
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
Ali, M., Garcia, P., Lunkes, L. P., Sciortino, A., Thomas, M. H., Heurtaux, T., et al. (2025). Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences. Acta Neuropathologica Communications. https://doi.org/10.1186/s40478-025-02013-z
Vancouver
Ali M, Garcia P, Lunkes LP, Sciortino A, Thomas MH, Heurtaux T, et al. Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences. Acta Neuropathologica Communications. 2025. doi:10.1186/s40478-025-02013-z. PMID: 40336141.
BibTeX
@article{ali2025-40336141,
author = {Ali, Muhammad and Garcia, Pierre and Lunkes, Laetitia P. and Sciortino, Alessia and Thomas, Mélanie H. and Heurtaux, Tony and Grzyb, Kamil and Halder, Rashi and others},
title = {{Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences}},
journal = {Acta Neuropathologica Communications},
year = {2025},
doi = {10.1186/s40478-025-02013-z},
pmid = {40336141},
url = {https://doi.org/10.1186/s40478-025-02013-z}
}
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