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Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer’s Disease
Anna Flavia Cantone, Chiara Burgaletto, Giulia Di Benedetto, Gabriella Gaudio, Cesarina Giallongo, Rosario Caltabiano, Giuseppe Broggi, Carlo Maria Bellanca et al.. Journal of Neuroimmune Pharmacology, 2025-02-07
Topic: Brain proteins, microglia and lab models
Abstract Alzheimer’s disease (AD) is the most common cause of dementia worldwide, characterized by accumulation of amyloid-β protein and hyperphosphorylated tau protein in the brain. Neuroinflammation, resulting from chronic activation of brain-resident innate immune cells as well as enhanced peripheral leukocyte access across the blood–brain barrier, crucially affects AD progression. In this context, TNFSF10, a cytokine substantially expressed in the AD brain, has been shown to modulate both the innate and the adaptive branches of the immune response in AD-related neuroinflammation. In this study, we explored whether a TNFSF10-neutralizing treatment could represent a tool to re-balance the overall overshooting inflammatory response in a mouse model of AD. Specifically, 3xTg-AD mice were treated sub-chronically with an anti-TNFSF10 monoclonal antibody for three months, and were then sacrificed at 15 months. TNFSF10 neutralization reduced the expression of the inflammatory marker CD86, inversely related to levels of the anti-inflammatory marker CD206 in the brain of 3xTg-AD mice, suggesting a switch of microglia towards a neuroprotective phenotype. Similar results were observed in the splenic macrophage population. Moreover, flow cytometry revealed a significant decrease of CD4+CD25+FOXP3+ T regulatory cells as well as reduced number of CD11b+LY6Chigh proinflammatory monocytes in both the brain and the spleen of 3xTg-AD mice treated with anti-TNFSF10 monoclonal antibody. Finally, the treatment resulted in lower count of splenic CD4+ and CD8+ T cells expressing PD1. The data suggest that TNFSF10 system-targeted treatment effectively restrain overshooting central and peripheral inflammation by rebalancing the overall immune response, mitigating the progression of AD pathology. Graphical Abstract
Key findings
- In this study, we explored whether a TNFSF10-neutralizing treatment could represent a tool to re-balance the overall overshooting inflammatory response in a mouse model of AD.
- Similar results were observed in the splenic macrophage population.
- Moreover, flow cytometry revealed a significant decrease of CD4+CD25+FOXP3+ T regulatory cells as well as reduced number of CD11b+LY6Chigh proinflammatory monocytes in both the brain and the spleen of 3xTg-AD mice treated with anti-TNFSF10 monoclonal antibody.
- The data suggest that TNFSF10 system-targeted treatment effectively restrain overshooting central and peripheral inflammation by rebalancing the overall immune response, mitigating the progression of AD pathology.
Why it matters
In a mouse model of Alzheimer's disease, blocking the immune signal TNFSF10 for three months shifted microglia and spleen macrophages toward a less inflammatory state and reduced certain inflammatory immune cells. These are animal findings, so it is not yet known whether this approach would help people.
Study details
- Evidence strengthLow
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, 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 (Journal of Neuroimmune Pharmacology) |
| Journal's citation record | 1 / 4 | Journal of Neuroimmune Pharmacology: journal h-index 108 (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 “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.4× 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 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Renato Bernardini: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Catania: institution h-index 518 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39918606) |
| Free to read | 2 / 2 | Free to read |
| Total | 35 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s11481-025-10177-7
- PubMed: 39918606
- Original source →
- Free full text: Journal of Neuroimmune Pharmacology →
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
Cantone, A. F., Burgaletto, C., Di Benedetto, G., Gaudio, G., Giallongo, C., Caltabiano, R., et al. (2025). Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer’s Disease. Journal of Neuroimmune Pharmacology. https://doi.org/10.1007/s11481-025-10177-7
Vancouver
Cantone AF, Burgaletto C, Di Benedetto G, Gaudio G, Giallongo C, Caltabiano R, et al. Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer’s Disease. Journal of Neuroimmune Pharmacology. 2025. doi:10.1007/s11481-025-10177-7. PMID: 39918606.
BibTeX
@article{cantone2025-39918606,
author = {Cantone, Anna Flavia and Burgaletto, Chiara and Di Benedetto, Giulia and Gaudio, Gabriella and Giallongo, Cesarina and Caltabiano, Rosario and Broggi, Giuseppe and Bellanca, Carlo Maria and others},
title = {{Rebalancing Immune Interactions within the Brain-Spleen Axis Mitigates Neuroinflammation in an Aging Mouse Model of Alzheimer’s Disease}},
journal = {Journal of Neuroimmune Pharmacology},
year = {2025},
doi = {10.1007/s11481-025-10177-7},
pmid = {39918606},
url = {https://doi.org/10.1007/s11481-025-10177-7}
}
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