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Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer's disease mouse model
Kiara Freitag, Nele Sterczyk, Sarah Wendlinger, Benedikt Obermayer, Julia Schulz, Vadim Farztdinov, Michael Mülleder, Markus Ralser et al.. Journal of neuroinflammation, 2022-07-02
Topic: Inflammation, microglia and astrocytes
Oral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation. Mechanistically, single nuclei sequencing revealed AD-associated microglia to be the main target of spermidine. This microglia population was characterized by increased AXL levels and expression of genes implicated in cell migration and phagocytosis. A subsequent proteome analysis of isolated microglia confirmed the anti-inflammatory and cytoskeletal effects of spermidine in APPPS1 mice. In primary microglia and astrocytes, spermidine-induced autophagy subsequently affected TLR3- and TLR4-mediated inflammatory processes, phagocytosis of Aβ and motility. Interestingly, spermidine regulated the neuroinflammatory response of microglia beyond transcriptional control by interfering with the assembly of the inflammasome. Our data highlight that the autophagy activator spermidine holds the potential to enhance Aβ degradation and to counteract glia-mediated neuroinflammation in AD pathology.
Key findings
- Oral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation.
- Mechanistically, single nuclei sequencing revealed AD-associated microglia to be the main target of spermidine.
- This microglia population was characterized by increased AXL levels and expression of genes implicated in cell migration and phagocytosis.
- A subsequent proteome analysis of isolated microglia confirmed the anti-inflammatory and cytoskeletal effects of spermidine in APPPS1 mice.
- In primary microglia and astrocytes, spermidine-induced autophagy subsequently affected TLR3- and TLR4-mediated inflammatory processes, phagocytosis of Aβ and motility.
Study details
- Evidence strengthLow
How this study scored 41/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuroinflammation) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2022 — within 6 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35780157) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Freitag, K., Sterczyk, N., Wendlinger, S., Obermayer, B., Schulz, J., Farztdinov, V., et al. (2022). Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer's disease mouse model. Journal of neuroinflammation. https://doi.org/10.1186/s12974-022-02534-7
Vancouver
Freitag K, Sterczyk N, Wendlinger S, Obermayer B, Schulz J, Farztdinov V, et al. Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer's disease mouse model. Journal of neuroinflammation. 2022. doi:10.1186/s12974-022-02534-7. PMID: 35780157.
BibTeX
@article{freitag2022-35780157,
author = {Freitag, Kiara and Sterczyk, Nele and Wendlinger, Sarah and Obermayer, Benedikt and Schulz, Julia and Farztdinov, Vadim and Mülleder, Michael and Ralser, Markus and others},
title = {{Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer's disease mouse model}},
journal = {Journal of neuroinflammation},
year = {2022},
doi = {10.1186/s12974-022-02534-7},
pmid = {35780157},
url = {https://doi.org/10.1186/s12974-022-02534-7}
}
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