Decreased Expression of Alzheimer’s Disease-Related Genes in Cancer May Contribute to the Inverse-Relationship-a Computational Study

Alzheimer's disease (AD) has been largely prevalent among the older population. With the increasing incidence of cancer over the years, scientists have explored the relationship between these two conditions which were formerly associated with aging. Interestingly, an inverse relationship between cancer and AD has been observed in large cohort studies which has garnered substantial interest. While this inverse relationship presents a fascinating scientific puzzle, there is limited data on the molecular mechanisms that govern this phenomenon. This study aims to investigate the fundamental molecular mechanisms driving the inverse association between AD and three common cancers: breast, prostate, and colorectal cancers. Gene expression data for AD were obtained from the Gene Expression Omnibus (GEO) repository, specifically the GSE122063 data set. Differentially expressed genes (DEGs) between AD and nondemented controls were identified using the GEO2R tool. Genes associated with breast, prostate, and colorectal cancer were obtained from the Genecards database. Shared genes between cancers and AD-upregulated genes were identified using the Venny 2.1 tool. The UALCAN analysis portal was used to evaluate the mRNA expression of shared genes in cancer types. The DAVID tool, ShinyGO and SRplotter tools were used for functional enrichment analyses and gene ontology annotations. We found 20 genes upregulated in AD but significantly downregulated in breast cancer, 11 significantly downregulated in prostate cancer and 5 genes downregulated in colon cancer. Key genes were involved in pathways related to muscle structure, DNA repair, protein stability, and gene expression regulation. Three (3) of these genes, <i>AQP1</i>, <i>CRYAB</i>, and <i>HSPB2</i>, were downregulated in all three cancers and may play an important role in reduced risk of cancer development while upregulated in AD. This study serves as a foundational effort to delve deeper into the molecular connections between AD and various cancer types, using the identified genes as a promising starting point for future experimental investigations to fully elucidate the mechanisms involved in the inverse interaction and protection of AD patients against cancer development.