Home › Research › Brain scans and imaging
Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology
Sun Y, Sommerville NR, Liu JYH, Ngan MP, Poon D, Ponomarev ED, Lu Z, Kung JSC et al.. The Journal of physiology, 2020-07-06
Topic: Amyloid, tau and blood-test diagnosis
Key points Alzheimer's disease (AD) patients and transgenic mice have beta-amyloid (Aβ) aggregation in the gastrointestinal (GI) tract. It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion-like properties. The present investigations demonstrate that Aβ injected into the GI tract of ICR mice is internalised into enteric cholinergic neurons; at 1 month, administration of Aβ into the body of the stomach and the proximal colon was observed to partly redistribute to the fundus and jejunum; at 1 year, vagal and cerebral β-amyloidosis was present, and mice exhibited GI dysfunction and cognitive deficits. These data reveal a previously undiscovered mechanism that potentially contributes to the development of AD. Abstract Alzheimer's disease (AD) is the most common age-related cause of dementia, characterised by extracellular beta-amyloid (Aβ) plaques and intracellular phosphorylated tau tangles in the brain. Aβ deposits have also been observed in the gastrointestinal (GI) tract of AD patients and transgenic mice, with overexpression of amyloid precursor protein. In the present studies, we investigate whether intra-GI administration of Aβ can potentially induce amyloidosis in the central nervous system (CNS) and AD-related pathology such as dementia. We micro-injected Aβ1-42 oligomers (4 μg per site, five sites) or vehicle (saline, 5 μl) into the gastric wall of ICR mice under general anaesthesia. Immunofluorescence staining and in vivo imaging showed that HiLyte Fluor 555-labelled Aβ1-42 had migrated within 3 h via the submucosa to nearby areas and was internalised into cholinergic neurons. At 1 month, HiLyte Fluor 555-labelled Aβ1-42 in the body of the stomach and proximal colon had partly re-distributed to the fundus and jejunum. At 1 year, the jejunum showed functional alterations in neuromuscular coupling (P < 0.001), and Aβ deposits were present in the vagus and brain, with animals exhibiting cognitive impairments in the Y-maze spontaneous alteration test (P < 0.001) and the novel object recognition test (P < 0.001). We found that enteric Aβ oligomers induce an alteration in gastric function, amyloidosis in the CNS, and AD-like dementia via vagal mechanisms. Our results suggest that Aβ load is likely to occur initially in the GI tract and may translocate to the brain, opening the possibility of new strategies for the early diagnosis and prevention of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Sun, Y., Sommerville, N. R., Liu, J. Y. H., Ngan, M. P., Poon, D., Ponomarev, E. D., et al. (2020). Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology. The Journal of physiology. https://doi.org/10.1113/jp279919
Vancouver
Sun Y, Sommerville NR, Liu JYH, Ngan MP, Poon D, Ponomarev ED, et al. Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology. The Journal of physiology. 2020. doi:10.1113/jp279919. PMID: 32617993.
BibTeX
@article{sun2020-32617993,
author = {Sun, Y. and Sommerville, N. R. and Liu, J. Y. H. and Ngan, M. P. and Poon, D. and Ponomarev, E. D. and Lu, Z. and Kung, J. S. C. and others},
title = {{Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology}},
journal = {The Journal of physiology},
year = {2020},
doi = {10.1113/jp279919},
pmid = {32617993},
url = {https://doi.org/10.1113/jp279919}
}
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.
Key findings
- Immunofluorescence staining and in vivo imaging showed that HiLyte Fluor 555-labelled Aβ1-42 had migrated within 3 h via the submucosa to nearby areas and was internalised into cholinergic neurons.
- We found that enteric Aβ oligomers induce an alteration in gastric function, amyloidosis in the CNS, and AD-like dementia via vagal mechanisms.
- Our results suggest that Aβ load is likely to occur initially in the GI tract and may translocate to the brain, opening the possibility of new strategies for the early diagnosis and prevention of AD.
New to this subject? Start with our plain-English guide: Brain scans & tests →
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 randomized / 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 multicenter 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 (The Journal of physiology) |
| 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32617993) |
| 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 →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Brain scans and imaging
Also tagged “function”
5 studies in the library carry the topic tag “function”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 5 tagged studies.