Yale-NUS College, 12 College Avenue West, Singapore, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Alzheimers Res Ther. 2024 Jun 7;16(1):123. doi: 10.1186/s13195-024-01487-8.
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.
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.
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.
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.
最近的报告表明，淀粉样β（Aβ）肽可能表现出朊病毒样的致病特性。已经有报道称，在使用受污染的器械进行手术、静脉或脑内接种后，Aβ肽可在鱼类、啮齿动物、灵长类动物和人类中传播，并导致相关病变。这让人担忧 Aβ肽也可能具有其他类似于朊病毒的特征，例如逃避消化过程。我们想知道 Aβ 聚集体是否可以通过摄入来传播。
我们利用表达易于聚集的人 Aβ肽的转基因黑腹果蝇系。将幼虫喂食给成年斑马鱼，采用两种喂养方案。第一种方案是 48 小时的短期高强度喂养，以确定在肠道中的传播和保留情况。第二种方案是长期方案，专门研究在大脑中的保留和积累情况。通过组织学、Western blot 和质谱分析检查肠道和脑组织。
尽管在饲料中很容易检测到，但在摄入后，在斑马鱼的肠道中均未检测到 Aβ 聚集体。此外，在长时间喂养后，没有检测到 Aβ 在脑组织中的积累或相关病变的发展。
虽然人类 Aβ 聚集体似乎不易通过摄入在物种间传播，但仍有两个方面需要进一步研究。首先，如果发生这种传播方式，其可能低于检测阈值，并且需要更长时间才能显现。另一种可能性是，人类 Aβ 肽不能在其他物种中引发自我传播或聚集。这两种可能性都需要进一步调查，同时要考虑到从用于食品工业的农业物种中传播的可能性。
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