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Updated: Jun 24, 2025
Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease
Published on: April 19, 2021
Evaluating the inter-species transmission risk of amyloid beta peptide aggregates via ingestion
Joshua Raine1,2, Nicholas Tolwinski1,3, Jan Gruber1,4,5
1Yale-NUS College, 12 College Avenue West, Singapore, Singapore.
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.
Insights
Ingesting amyloid beta (Aβ) aggregates did not lead to transmission or brain accumulation in zebrafish, suggesting oral transmission is unlikely. Further research is needed to confirm if Aβ transmission via food is possible.
Area of Science:
- Neuroscience
- Biochemistry
- Prion Biology
Background:
- Recent reports indicate amyloid beta (Aβ) peptides may possess prion-like properties, with transmission observed via surgical instruments and inoculation in various species.
- This raises concerns about Aβ's potential to evade digestion and spread through ingestion, similar to prions.
- The study investigates the possibility of Aβ aggregate transmission via oral consumption.
Discussion:
- Transgenic Drosophila melanogaster expressing human Aβ were fed to zebrafish to assess oral transmission.
- Two feeding schemes were employed: short-term high-intensity and long-term exposure.
- Gut and brain tissues were analyzed using histology, western blotting, and mass spectrometry.
Key Insights:
- No detectable Aβ aggregates were found in zebrafish guts after ingestion, even when present in the feed.
- Prolonged feeding did not result in Aβ accumulation in the brain or associated pathologies.
- These findings suggest that oral transmission of Aβ aggregates across species is not readily occurring.
Outlook:
- While direct oral transmission appears unlikely, low-level or delayed manifestation cannot be ruled out.
- The inability of human Aβ to trigger self-propagation in other species may explain the lack of transmission.
- Further investigation is required, considering potential transmission from agricultural species in the food industry.
