Joshua Raine, Nicholas Tolwinski, Jan Gruber, Ajay S Mathuru
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引用次数: 0
Abstract
Background: Recent reports suggest that amyloid beta (Aβ) peptides can exhibit prion-like pathogenic properties. Transmission of Aβ peptide and the development of associated pathologies after surgeries with contaminated instruments and intravenous or intracerebral inoculations have now been reported across fish, rodents, primates, and humans. This raises a worrying prospect of Aβ peptides also having other characteristics typical of prions, such as evasion of the digestive process. We asked if such transmission of Aβ aggregates via ingestion was possible.
Methods: We made use of a transgenic Drosophila melanogaster line expressing human Aβ peptide prone to aggregation. Fly larvae were fed to adult zebrafish under two feeding schemes. The first was a short-term, high-intensity scheme over 48 h to determine transmission and retention in the gut. The second, long-term scheme specifically examined retention and accumulation in the brain. The gut and brain tissues were examined by histology, western blotting, and mass spectrometric analyses.
Results: None of the analyses could detect Aβ aggregates in the guts of zebrafish following ingestion, despite being easily detectable in the feed. Additionally, there was no detectable accumulation of Aβ in the brain tissue or development of associated pathologies after prolonged feeding.
Conclusions: While human Aβ aggregates do not appear to be readily transmissible by ingestion across species, two prospects remain open. First, this mode of transmission, if occurring, may stay below a detectable threshold and may take much longer to manifest. A second possibility is that the human Aβ peptide is not able to trigger self-propagation or aggregation in other species. Either possibility requires further investigation, taking into account the possibility of such transmission from agricultural species used in the food industry.
期刊介绍:
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.