Biological and disease hallmarks of Alzheimer’s disease defined by Alzheimer’s disease genes

Abstract

An increasing number of genes associated with Alzheimer’s disease (AD genes) have been reported. However, there is a lack of an overview of the genetic relationship between AD and age-related comorbidities, such as hypertension, myocardial infarction, and diabetes, among others. Previously, we used Reactome analysis in conjunction with the AD genes to identify both the biological pathways and the neurological diseases. Here we provide systematic updates on the genetic and disease hallmarks defined by AD genes. The analysis identified 50 pathways (defined as biological hallmarks). Of them, we have successfully compiled them into a total of 11 biological hallmarks, including 6 existing hallmarks and 5 newly updated hallmarks. The AD genes further identified 20 diverse diseases (defined as disease hallmarks), summarized into three major categories: (1) existing hallmarks, including neurological diseases; (2) newly identified hallmarks, including common age-related diseases such as diabetes, hypertension, other cardiovascular diseases, and cancers; (3) and other health conditions; note that cancers reportedly have an inverse relation with AD. We previously suggested that a single gene is associated with multiple neurological diseases, and we are further extending the finding that AD genes are associated with common age-related comorbidities and others. This study indicates that the heterogeneity of Alzheimer’s disease predicts complex clinical presentations in people living with AD. Taken together, the genes define AD as a part of age-related comorbidities with shared biological mechanisms and may raise awareness of a healthy lifestyle as potential prevention and treatment of the comorbidities.