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bioRxiv · 10.1101/2023.08.03.551437

Evaluating the transmission risk of amyloid beta peptide via ingestion

Raine, J.·Tolwinski, N.·Gruber, J.·Mathuru, A.
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Abstract

BackgroundRecent reports suggest that amyloid beta (A{beta}) peptides can exhibit prion-like pathogenic properties. Transmission of A{beta} 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 A{beta} peptides also having other characteristics typical of prions, such as evasion of the digestive process. We asked if such transmission of A{beta} aggregates via ingestion was possible. MethodsWe made use of a transgenic Drosophila melanogaster line expressing human A{beta} 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 hours 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. ResultsNone of the analyses could detect A{beta} aggregates in the guts of zebrafish following ingestion, despite being easily detectable in the feed. Additionally, there was no detectable accumulation of A{beta} in the brain tissue or development of associated pathologies after prolonged feeding. ConclusionsWhile human A{beta} 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 A{beta} peptide may not be 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.

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Raine, J., Tolwinski, N., Gruber, J., Mathuru, A.. 2023-08-06. Evaluating the transmission risk of amyloid beta peptide via ingestion. https://doi.org/10.1101/2023.08.03.551437

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