Background and Aim: Microbiota-derived metabolites could alter the brain tissue toward the neurodegeneration disease. It was accepted as a new hypothesis for Alzheimer disease. One of crucial metabolites is propionic acid that associated with several dysfunctionalities in vivo and in vitro. Methods: PPA associated genes and AD genes were corporate from multi-source public databases, Coremine search engine, and GEO. The common genes screened for diseases relation retrieved from DisGeNet in Enrich database. The String database was applied to Gene Ontology and KEEG pathway analysis. To find hubs, and bottlenecks used the network that provided by Cytoscape. To assess subnetworks and get seed genes, used the MCODE plugin. Results: In this study, we selected the gene interacted PPA and compromise AD from public database(CTD,Coremine, GeneCards), and GEO. The obtained data were analyzed for gene onthology,keeg pathway, and network to find the mechanism related APP.۲۸۴ Gene related APP could enrich the BP and pathways that cover the most AD hallmark such as amyloid formation, apoptosis, proliferation, inflammation, immune system. PPA AD genes shared in neoplasm disease, autism, schizophrenia, and several pathogeneses. Conclusion: Amongst all genes associated with PPA and AD, ۲۸۴ genes to be shared by searching databases and were subjected for further analysis. PPA-AD genes mainly involved in cancer, bacterial and virus Infection, and neurological and non-neurological diseases. GO, and pathway analysis covered the most AD hallmark, such as amyloid formation, apoptosis, proliferation, inflammation, and immune system. Network analysis revealed hub and bottleneck genes. MCODE analysis also indicated the seed genes represented in the significant sub-networks. ICAM۱ was the common gene between a hub, bottlenecks, and seed genes. PPA related genes implicated in AD act through pathways initiate neuronal cell death. In sum, up AD-APP shared genes revealed evidence that supports the idea PPA secreted from bacteria could alter brain physiology toward the emerging AD signs. This idea needs to confirm by more future investigation in animal models.
