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Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain
Yuhai Zhao, Lin Cong, Vivian R. Jaber, Walter J. Lukiw. Frontiers in Immunology, 2017-09-04
Topic: Gut, metabolism and diet
Abundant clinical, epidemiological, imaging, genetic, molecular and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer’s disease (AD) brain. Despite many years of intense study the origin and molecular mechanics of these AD-relevant pathogenic signals are still not well understood. Here we provide evidence that an intensely pro-inflammatory bacterial lipopolysaccharide (LPS), part of a complex mixture of pro-inflammatory neurotoxins arising from abundant Gram-negative bacilli of the human gastrointestinal (GI) tract, are abundant in AD affected brain neocortex and hippocampus. For the first time we provide evidence that LPS immuno-histochemical signals appear to aggregate in clumps in the parenchyma in control brains, and in AD about 75% of anti-LPS signals were clustered around the periphery of DAPI-stained nuclei. As LPS is an abundant secretory-product of Gram-negative bacilli resident in the human GI-tract, these observations suggest (i) that a major source of pro-inflammatory signals in AD brain may originate from internally-derived noxious exudates of the GI-tract microbiome; (ii) that due to aging, vascular deficits or degenerative disease these neurotoxic molecules may ‘leak’ into the systemic circulation, cerebral vasculature and on into the brain; and (iii) that this internal source of microbiome-derived neurotoxins may play a particularly strong role in shaping the human immune system and contributing to neural degeneration, particularly in the aging CNS. This ‘Perspectives’ paper will further highlight some very recent developments that implicate GI-tract microbiome-derived LPS as an important contributor to inflammatory-neurodegeneration in the AD brain
Key findings
- Abundant clinical, epidemiological, imaging, genetic, molecular and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer’s disease (AD) brain.
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, studied in people 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 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Immunology) |
| 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 | 2017 — 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 | 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 | — / 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 28928740) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 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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APA 7th
Zhao, Y., Cong, L., Jaber, V. R., & Lukiw, W. J. (2017). Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2017.01064
Vancouver
Zhao Y, Cong L, Jaber VR, Lukiw WJ. Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain. Frontiers in Immunology. 2017. doi:10.3389/fimmu.2017.01064. PMID: 28928740.
BibTeX
@article{zhao2017-28928740,
author = {Zhao, Yuhai and Cong, Lin and Jaber, Vivian R. and Lukiw, Walter J.},
title = {{Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain}},
journal = {Frontiers in Immunology},
year = {2017},
doi = {10.3389/fimmu.2017.01064},
pmid = {28928740},
url = {https://doi.org/10.3389/fimmu.2017.01064}
}