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Tau Pathology Drives Disease‐Associated Astrocyte Reactivity in Salt‐Induced Neurodegeneration
Tongyu Rui, He‐Zhou Huang, Kai Zheng, Hong‐Wei Fan, Juan Zhang, Ziyuan Guo, Heng‐Ye Man, Nadezda A. Brazhe et al.. Advanced Science, 2025-01-24
Topic: Brain proteins, microglia and lab models
Dietary high salt intake is increasingly recognized as a risk factor for cognitive decline and dementia, including Alzheimer's disease (AD). Recent studies have identified a population of disease-associated astrocytes (DAA)-like astrocytes closely linked to amyloid deposition and tau pathology in an AD mouse model. However, the presence and role of these astrocytes in high-salt diet (HSD) models remain unexplored. In this study, it is demonstrated that HSD significantly induces enhanced reactivity of DAA-like astrocytes in the hippocampal CA3 region of mice, with this reactivity being critically dependent on neuronal tau pathology. Neuronal tau pathology activates adenosine A1R signaling, exacerbating tau pathology by inhibiting the Cers1 pathway, which sustains astrocyte reactivity. Additionally, neurons burdened with tau pathology promote astrocyte reactivity via releasing Proteins Associated with Promoting DAA-like Astrocyte Reactivity (PAPD), with Lcn2 playing a pivotal role. Knockout of Lcn2 or its receptor 24p3R significantly mitigates HSD-induced DAA reactivity and neuroinflammation. These findings suggest a vicious cycle between tau pathology and A1R signaling, driving DAA-like astrocyte reactivity. Targeting the Tau-A1R axis may provide a novel therapeutic strategy for reducing HSD-induced neuroinflammation and cognitive deficits.
Key findings
- In this study, it is demonstrated that HSD significantly induces enhanced reactivity of DAA-like astrocytes in the hippocampal CA3 region of mice, with this reactivity being critically dependent on neuronal tau pathology.
- Additionally, neurons burdened with tau pathology promote astrocyte reactivity via releasing Proteins Associated with Promoting DAA-like Astrocyte Reactivity (PAPD), with Lcn2 playing a pivotal role.
- Knockout of Lcn2 or its receptor 24p3R significantly mitigates HSD-induced DAA reactivity and neuroinflammation.
- These findings suggest a vicious cycle between tau pathology and A1R signaling, driving DAA-like astrocyte reactivity.
Why it matters
In mice on a high-salt diet, tau pathology drove reactive astrocytes in the hippocampus, and removing Lcn2 or its receptor reduced this reactivity and neuroinflammation. This is animal work suggesting a possible target, not evidence that it helps people.
Study details
- Evidence strengthLow
How this study scored 42/100
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 (Advanced Science) |
| Journal's citation record | 3 / 4 | Advanced Science: journal h-index 282 (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 | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.8× 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 | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ling‐Qiang Zhu: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Boston University: institution h-index 1,456 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39853966) |
| 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
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
Rui, T., Huang, H., Zheng, K., Fan, H., Zhang, J., Guo, Z., et al. (2025). Tau Pathology Drives Disease‐Associated Astrocyte Reactivity in Salt‐Induced Neurodegeneration. Advanced Science. https://doi.org/10.1002/advs.202410799
Vancouver
Rui T, Huang H, Zheng K, Fan H, Zhang J, Guo Z, et al. Tau Pathology Drives Disease‐Associated Astrocyte Reactivity in Salt‐Induced Neurodegeneration. Advanced Science. 2025. doi:10.1002/advs.202410799. PMID: 39853966.
BibTeX
@article{rui2025-39853966,
author = {Rui, Tongyu and Huang, He‐Zhou and Zheng, Kai and Fan, Hong‐Wei and Zhang, Juan and Guo, Ziyuan and Man, Heng‐Ye and Brazhe, Nadezda A. and others},
title = {{Tau Pathology Drives Disease‐Associated Astrocyte Reactivity in Salt‐Induced Neurodegeneration}},
journal = {Advanced Science},
year = {2025},
doi = {10.1002/advs.202410799},
pmid = {39853966},
url = {https://doi.org/10.1002/advs.202410799}
}
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