The relationship between the two age-related diseases namely, Alzheimer's disease (AD) and type II diabetes mellitus (T2DM), is gaining much attention in research because of the alarming forecast on both increasing incidence and economic burden. Recent research studies have identified some of the existing links, between AD and T2DM, such as the dysfunctional glucose metabolism and insulin signaling, stress and inflammation, defective protein processing and the role of advanced glycation end products. It is, therefore, crucial to understand the cellular and molecular mechanisms to identify the common linking mechanisms involved in the pathogenesis of both AD and T2DM. Genome wide association studies may lead to identification of novel targets and provide clues for possible interventional strategies to limit the progression of these two age-related diseases. Hence, the purpose of the present review is to provide an update, on the various possible linking cellular and molecular mechanisms, including our experience on the use of high throughput applications to investigate the molecular mechanisms underneath the neurodegeneration in animal models. Besides, using this knowledge-driven approach, we discuss how the current technological advancements can effectively be used to identify possible associations between these age-related diseases.