Computational identification of amyloid-mimicking microbial peptides with predicted MHC-II presentation relevance to Alzheimer’s diseaseDownload PDF Download PDF ArticleOpen accessPublished: 30 July 2026Weichen Gong1,2 npj Systems Biology and Applications (2026) Cite this article We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.AbstractAccumulating evidence suggests a link between gut microbiota, host immunity, and Alzheimer’s disease (AD), while specific MHC-II alleles have been associated with disease susceptibility or protection. Here, we applied a computational framework to investigate whether microbial proteins contain amyloid-like motifs capable of interacting with Aβ42 and whether such peptides are differentially presented by distinct MHC-II alleles. We identified an aggregation-prone core within Aβ42 and screened AD-associated gut microbial proteomes to detect homologous peptide motifs. Predicted antigen presentation was evaluated using IEDB, and potential co-aggregation was assessed in silico. We identified microbial amyloid-mimicking peptides predicted to be presented by AD-associated MHC-II alleles, whereas fewer candidate peptides were identified for the protective alleles. Several peptides shared sequence similarity with Aβ42 aggregation motifs and demonstrated predicted structural compatibility for co-aggregation. These findings suggest a potential link between microbial peptide mimicry, antigen presentation, and amyloid biology. This study is computational and hypothesis-generating, providing a systems-level framework for understanding microbiota–immune interactions in AD.SubjectsComputational biology and bioinformaticsImmunologyMicrobiologyAcknowledgementsThis study was supported by the Japan Society for the Promotion of Science KAKENHI (grant number 25K23670). The funders had no role in the review design, decision to publish, or manuscript preparation. This work was supported by publication funding from the Tohoku University APC Support Program (APC Kakudai).Author informationAuthors and AffiliationsLaboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai, JapanWeichen GongLivestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, JapanWeichen GongAuthorsWeichen GongView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Weichen Gong.Ethics declarationsCompeting interestsThe author declares no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsAbout this article