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Astrocytes upregulate interleukin-15 in response to neuroinflammation during Alzheimer's disease
Benjamin C. F. Shaw, Kaitlin E. Kaiser, Brandon C. Smith, J Payton Timken, Antoine Louveau, Jessica Lynn Williams. Journal of Alzheimer s Disease, 2025-11-05
Topic: Brain proteins, microglia and lab models
Background Interleukin (IL)-15 is a pleiotropic cytokine linked to cognition that is increased in the cerebrospinal fluid of Alzheimer's disease (AD) patients; however, the cellular source of IL-15 and IL-15-sensing cells in AD has not been described. Objective We sought to determine the cell types responsible for IL-15 secretion in AD and their spatial relationship with amyloid-β (Aβ) pathology. Methods We performed immunofluorescent labeling of human postmortem frontal cortex tissue from cognitively intact and dementia patients and used RNA-sequencing and in vitro assays to confirm the stimulus and source of IL-15. We also assessed the hippocampus of 6–7-month-old 5xFAD mice for cytokine levels using multiplex ELISA. Results In the prefrontal cortex of AD patients, we observed increased IL-15 colocalization with GFAP + astrocytes ( p = 0.0181) near Aβ plaques and demonstrate that astrocytes, but not neurons, upregulate IL-15 in response to interferon-γ and tumor necrosis factor-α in vitro ( p = 0.0003 and p < 0.0001, respectively). We also show that neurons express increased IL2Rγ and IL2Rβ colocalization as Braak score increases ( p = 0.0002) and that IL-15 is increased in the 5xFAD hippocampus compared to control animals ( p = 0.0021). Conclusions Astrocytes are a source of IL-15 in AD, particularly near localized Aβ pathology, and neurons are poised to respond. The 5xFAD model recapitulates the hippocampal inflammatory milieu associated with AD and may be a useful tool to study the role of IL-15 in the context of Aβ pathology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Shaw, B. C. F., Kaiser, K. E., Smith, B. C., Timken, J. P., Louveau, A., & Williams, J. L. (2025). Astrocytes upregulate interleukin-15 in response to neuroinflammation during Alzheimer's disease. Journal of Alzheimer s Disease. https://doi.org/10.1177/13872877251393275
Vancouver
Shaw BCF, Kaiser KE, Smith BC, Timken JP, Louveau A, Williams JL. Astrocytes upregulate interleukin-15 in response to neuroinflammation during Alzheimer's disease. Journal of Alzheimer s Disease. 2025. doi:10.1177/13872877251393275. PMID: 41191004.
BibTeX
@article{shaw2025-41191004,
author = {Shaw, Benjamin C. F. and Kaiser, Kaitlin E. and Smith, Brandon C. and Timken, J Payton and Louveau, Antoine and Williams, Jessica Lynn},
title = {{Astrocytes upregulate interleukin-15 in response to neuroinflammation during Alzheimer's disease}},
journal = {Journal of Alzheimer s Disease},
year = {2025},
doi = {10.1177/13872877251393275},
pmid = {41191004},
url = {https://doi.org/10.1177/13872877251393275}
}
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
- Results In the prefrontal cortex of AD patients, we observed increased IL-15 colocalization with GFAP + astrocytes ( p = 0.0181) near Aβ plaques and demonstrate that astrocytes, but not neurons, upregulate IL-15 in response to interferon-γ and tumor necrosis factor-α in vitro ( p = 0.0003 and p < 0.0001, respectively).
- We also show that neurons express increased IL2Rγ and IL2Rβ colocalization as Braak score increases ( p = 0.0002) and that IL-15 is increased in the 5xFAD hippocampus compared to control animals ( p = 0.0021).
- The 5xFAD model recapitulates the hippocampal inflammatory milieu associated with AD and may be a useful tool to study the role of IL-15 in the context of Aβ pathology.
Why it matters
In brain tissue from people with Alzheimer's disease and in mice, astrocytes near amyloid plaques produced more of the immune signal IL-15, and neurons appeared able to respond to it. This identifies a possible inflammatory pathway but does not yet show that targeting it helps patients.
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, 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 (Journal of Alzheimer s Disease) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (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 | 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 0.3× 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 | 2 / 4 | Last-listed author Jessica Lynn Williams: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Cleveland Clinic: institution h-index 1,139 (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 41191004) |
| Free to read | 2 / 2 | Free to read |
| Total | 33 / 100 | — |
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