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Inflammation induced by infection potentiates tau pathological features in transgenic mice
Sy M, Kitazawa M, Medeiros R, Whitman L, Cheng D, Lane TE, Laferla FM.. The American journal of pathology, 2011-04-30
Topic: Inflammation, microglia and astrocytes
Comorbidities that promote the progression of Alzheimer's disease (AD) remain to be uncovered and evaluated in animal models. Because elderly individuals are vulnerable to viral and bacterial infections, these microbial agents may be considered important comorbidities that could potentiate an already existing and tenuous inflammatory condition in the brain, accelerating cognitive decline, particularly if the cellular and molecular mechanisms can be defined. Researchers have recently demonstrated that triggering inflammation in the brain exacerbates tau pathological characteristics in animal models. Herein, we explore whether inflammation induced via viral infection, compared with inflammation induced via bacterial lipopolysaccharide, modulates AD-like pathological features in the 3xTg-AD mouse model and provide evidence to support the hypothesis that infectious agents may act as a comorbidity for AD. Our study shows that infection-induced acute or chronic inflammation significantly exacerbates tau pathological characteristics, with chronic inflammation leading to impairments in spatial memory. Tau phosphorylation was increased via a glycogen synthase kinase-3β-dependent mechanism, and there was a prominent shift of tau from the detergent-soluble to the detergent-insoluble fraction. During chronic inflammation, we found that inhibiting glycogen synthase kinase-3β activity with lithium reduced tau phosphorylation and the accumulation of insoluble tau and reversed memory impairments. Taken together, infectious agents that trigger central nervous system inflammation may serve as a comorbidity for AD, leading to cognitive impairments by a mechanism that involves exacerbation of tau pathological characteristics.
Key findings
- Researchers have recently demonstrated that triggering inflammation in the brain exacerbates tau pathological characteristics in animal models.
- Herein, we explore whether inflammation induced via viral infection, compared with inflammation induced via bacterial lipopolysaccharide, modulates AD-like pathological features in the 3xTg-AD mouse model and provide evidence to support the hypothesis that infectious agents may act as a comorbidity for AD.
- Our study shows that infection-induced acute or chronic inflammation significantly exacerbates tau pathological characteristics, with chronic inflammation leading to impairments in spatial memory.
- During chronic inflammation, we found that inhibiting glycogen synthase kinase-3β activity with lithium reduced tau phosphorylation and the accumulation of insoluble tau and reversed memory impairments.
- Taken together, infectious agents that trigger central nervous system inflammation may serve as a comorbidity for AD, leading to cognitive impairments by a mechanism that involves exacerbation of tau pathological characteristics.
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Study details
- Evidence strengthLow
How this study scored 36/100
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 and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of pathology) |
| 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 | 1 / 5 | 2011 — within 20 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 “transgenic”) — 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 21531375) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 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 7 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
Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., et al. (2011). Inflammation induced by infection potentiates tau pathological features in transgenic mice. The American journal of pathology. https://doi.org/10.1016/j.ajpath.2011.02.012
Vancouver
Sy M, Kitazawa M, Medeiros R, Whitman L, Cheng D, Lane TE, et al. Inflammation induced by infection potentiates tau pathological features in transgenic mice. The American journal of pathology. 2011. doi:10.1016/j.ajpath.2011.02.012. PMID: 21531375.
BibTeX
@article{sy2011-21531375,
author = {Sy, M. and Kitazawa, M. and Medeiros, R. and Whitman, L. and Cheng, D. and Lane, T. E. and Laferla, F. M.},
title = {{Inflammation induced by infection potentiates tau pathological features in transgenic mice}},
journal = {The American journal of pathology},
year = {2011},
doi = {10.1016/j.ajpath.2011.02.012},
pmid = {21531375},
url = {https://doi.org/10.1016/j.ajpath.2011.02.012}
}