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Targeting the miR‐96‐5p/Cathepsin B Pathway to Alleviate Neuron‐Derived Neuroinflammation in Alzheimer's Disease
Kai Zheng, He‐Zhou Huang, Dan Liu, Nadezda A. Brazhe, Jiajie Chen, Ling‐Qiang Zhu. MedComm, 2025-09-01
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) is one of the leading causes of dementia in the elderly, and no effective treatment is currently available. Cathepsin B (CTSB) is involved in key pathological processes of AD, but the underlying mechanisms and its relevance to AD diagnosis and treatment remain unclear. In the present study, we found that CTSB expression was abnormally elevated in the hippocampus of 3×Tg mice and was regulated by miR-96-5p. Abnormalities in the miR-96-5p/CTSB signaling pathway were detected in the serum of both mild cognitive impairment and AD patients, and the combination of serum miR-96-5p and CTSB demonstrated strong diagnostic efficacy for cognitive impairment (AUC = 0.7536). Abnormalities in the miR-96-5p/CTSB signaling pathway in AD may be associated with Aβ pathology, and neuronal CTSB can be released extracellularly to reactivate adjacent astrocytes. Ultimately, the reconstitution of the miR-96-5p/CTSB signaling pathway effectively rescued astrocyte reactivity and memory impairment in AD. Our findings suggest that the neuron-derived inflammatory mediator CTSB reactivates adjacent astrocytes and mediates memory impairment in early AD. The combination of serum miR-96-5p and CTSB represents potential serum biomarkers for cognitive impairment, and targeting the neuronal miR-96-5p/CTSB pathway may serve as a promising therapeutic strategy for AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zheng, K., Huang, H., Liu, D., Brazhe, N. A., Chen, J., & Zhu, L. (2025). Targeting the miR‐96‐5p/Cathepsin B Pathway to Alleviate Neuron‐Derived Neuroinflammation in Alzheimer's Disease. MedComm. https://doi.org/10.1002/mco2.70368
Vancouver
Zheng K, Huang H, Liu D, Brazhe NA, Chen J, Zhu L. Targeting the miR‐96‐5p/Cathepsin B Pathway to Alleviate Neuron‐Derived Neuroinflammation in Alzheimer's Disease. MedComm. 2025. doi:10.1002/mco2.70368. PMID: 40919134.
BibTeX
@article{zheng2025-40919134,
author = {Zheng, Kai and Huang, He‐Zhou and Liu, Dan and Brazhe, Nadezda A. and Chen, Jiajie and Zhu, Ling‐Qiang},
title = {{Targeting the miR‐96‐5p/Cathepsin B Pathway to Alleviate Neuron‐Derived Neuroinflammation in Alzheimer's Disease}},
journal = {MedComm},
year = {2025},
doi = {10.1002/mco2.70368},
pmid = {40919134},
url = {https://doi.org/10.1002/mco2.70368}
}
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
- In the present study, we found that CTSB expression was abnormally elevated in the hippocampus of 3×Tg mice and was regulated by miR-96-5p.
- Abnormalities in the miR-96-5p/CTSB signaling pathway were detected in the serum of both mild cognitive impairment and AD patients, and the combination of serum miR-96-5p and CTSB demonstrated strong diagnostic efficacy for cognitive impairment (AUC = 0.7536).
- Abnormalities in the miR-96-5p/CTSB signaling pathway in AD may be associated with Aβ pathology, and neuronal CTSB can be released extracellularly to reactivate adjacent astrocytes.
- Our findings suggest that the neuron-derived inflammatory mediator CTSB reactivates adjacent astrocytes and mediates memory impairment in early AD.
Why it matters
In mice and patient serum samples, the miR-96-5p/CTSB pathway was linked to neuroinflammation and cognitive impairment, and targeting it rescued memory impairment in mice. The serum marker combination showed diagnostic potential, but this is not yet a proven treatment or cure for Alzheimer's disease in people.
Study details
- Effect sizeAUC = 0.7536
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, 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 (MedComm) |
| Journal's citation record | 1 / 4 | MedComm: journal h-index 83 (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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.6× 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 3 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 | Huazhong University of Science and Technology: institution h-index 934 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40919134) |
| Free to read | 2 / 2 | Free to read |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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