Association between behavioural risks and Alzheimer's disease: Elucidated with an integrated analysis of gene expression patterns and molecular mechanisms

Alzheimer's disease (AD) remains a global health challenge. Previous studies have reported linkages between AD and multiple behavioural risk exposures, however, the underlying biological mechanisms and crucial genes of gene expression patterns driven by behavioural risks on the onset or progression of AD remains ambiguous. In this study, we performed an integrated analysis on the influence of behavioural risks including smoking, excessive alcohol consumption, physical inactivity, and non-healthy dietary pattern on AD with a comprehensive strategy. Our results demonstrated that multiple behavioural risk exposures could independently or collectively influence diverse hierarchical levels of gene expression patterns through multiple biological mechanisms such as Wnt, mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), nuclear factor (NF)-κB, phosphatidylinositol 3-kinase (PI3K)-Akt, and insulin (INS) signalling pathways-mediated pathological processes, thereby prodromally or intermediately impacting AD. Our study provided insights into understanding the association of behavioural risk exposures with AD and informative support for further studies. [Display omitted] •Common behavioural risks may influence Alzheimer's disease (AD).•The changes in gene expression patterns by behavioural risks for AD were identified.•The integrated biological mechanisms of behavioural risks on AD were investigated.•The interactions of crucial genes of behavioural risks for AD were uncovered.•Diverse hierarchical levels of genes impacting AD by behavioural risks were revealed.