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Metabolic syndrome exacerbates amyloid pathology in a comorbid Alzheimer's mouse model
Alpna Tyagi, Carol Mirita, Nadine Taher, Iman Shah, Emily Moeller, Anit Tyagi, Thomas Chong, Subbiah Pugazhenthi. Biochimica et biophysica acta. Molecular basis of disease, 2020-05-30
Topic: Gut, metabolism and diet
Alzheimer's disease (AD) often coexists with other aging-associated diseases including obesity, diabetes, hypertension, and cardiovascular diseases. The early stage of these comorbidities is known as metabolic syndrome (MetS) which is highly prevalent in mid-life. An important cause of MetS is the deficiency of SIRT3, a mitochondrial deacetylase which enhances the functions of critical mitochondrial proteins, including metabolic enzymes, by deacetylation. Deletion of Sirt3 gene has been reported to result in the acceleration of MetS. In a recently published study, we demonstrated in the brain of Sirt3-/- mice, downregulation of metabolic enzymes, insulin resistance and elevation of inflammatory markers including microglial proliferation. These findings suggested a novel pathway that could link SIRT3 deficiency to neuroinflammation, an important cause of Alzheimer's pathogenesis. Therefore, we hypothesized that MetS and amyloid pathology may interact through converging pathways of insulin resistance and neuroinflammation in comorbid AD. To investigate these interactions, we crossed Sirt3-/- mice with APP/PS1 mice and successfully generated APP/PS1/Sirt3-/- mice with amyloid pathology and MetS. In these comorbid AD mice, we observed exacerbation of insulin resistance, glucose intolerance, amyloid plaque deposition, markers of neuroinflammation, including elevated expression of IL-1β, TNF-α and Cox-2 at 8 months of age. There was also increased microglial proliferation and activation. Our observations suggest a novel mechanism by which MetS may interact with amyloid pathology during the cellular phase of AD. Therapeutic targeting of SIRT3 in AD with comorbidities may produce beneficial effects.
Key findings
- Deletion of Sirt3 gene has been reported to result in the acceleration of MetS.
- In a recently published study, we demonstrated in the brain of Sirt3-/- mice, downregulation of metabolic enzymes, insulin resistance and elevation of inflammatory markers including microglial proliferation.
- These findings suggested a novel pathway that could link SIRT3 deficiency to neuroinflammation, an important cause of Alzheimer's pathogenesis.
- In these comorbid AD mice, we observed exacerbation of insulin resistance, glucose intolerance, amyloid plaque deposition, markers of neuroinflammation, including elevated expression of IL-1β, TNF-α and Cox-2 at 8 months of age.
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Study details
- Evidence strengthLow
How this study scored 39/100
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 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochimica et biophysica acta. Molecular basis of disease) |
| 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 | 2 / 5 | 2020 — within 10 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 32485218) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Tyagi, A., Mirita, C., Taher, N., Shah, I., Moeller, E., Tyagi, A., et al. (2020). Metabolic syndrome exacerbates amyloid pathology in a comorbid Alzheimer's mouse model. Biochimica et biophysica acta. Molecular basis of disease. https://doi.org/10.1016/j.bbadis.2020.165849
Vancouver
Tyagi A, Mirita C, Taher N, Shah I, Moeller E, Tyagi A, et al. Metabolic syndrome exacerbates amyloid pathology in a comorbid Alzheimer's mouse model. Biochimica et biophysica acta. Molecular basis of disease. 2020. doi:10.1016/j.bbadis.2020.165849. PMID: 32485218.
BibTeX
@article{tyagi2020-32485218,
author = {Tyagi, Alpna and Mirita, Carol and Taher, Nadine and Shah, Iman and Moeller, Emily and Tyagi, Anit and Chong, Thomas and Pugazhenthi, Subbiah},
title = {{Metabolic syndrome exacerbates amyloid pathology in a comorbid Alzheimer's mouse model}},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
year = {2020},
doi = {10.1016/j.bbadis.2020.165849},
pmid = {32485218},
url = {https://doi.org/10.1016/j.bbadis.2020.165849}
}
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