Integrated Analysis of the Association Between Alzheimer`s Disease (AD) and Cardiovascular Disease (CVD)

Abstract Alzheimer’s Disease (AD), the sixth leading cause of death in the US, and cardiovascular disease (CVD), the first leading cause of death in the US, are frequently associated. Past studies hypothesize that amyloid deposits damage organs, causing this association. Examining how vascular factors can influence AD pathogenesis can help in understanding the link between the blood to the brain, which can provide alternative paths of exploration for disease treatment. This study analyzes gene expression and shared biological processes between AD and CVD, specifically myocardial infarction and heart failure, via bioinformatic approaches and published datasets from the Gene Expression Omnibus (GEO). First, 73 differentially expressed genes (DEGs) were identified among four datasets using blood samples from AD and CVD patients. Panther’s Gene Ontology Analysis validated several biological processes such as xylulose biosynthetic process and toll-like receptor TLR1:TLR2 signaling pathway along with molecular functions, cellular components, and pathways to be significantly enriched in the list of 73 DEGs. Analysis of protein-protein interactions and the associated gene network indicated that from the list of 73 DEGs, only six (MAPK14, TLR2, HCK, GRB2, PRKCD, PTPN6) had eight or more degrees. Next, those six genes were identified in a normalized dataset containing different brain regions of AD and non-AD patients. Two-sample t-tests for differences in mean showed statistically significant differences in GRB2 and PRKCD, supporting a blood-brain relationship in the association between AD and CVD. This study can help in developing new medications to target AD and CVD susceptible genes.