Diabetes Mellitus-related Pathogeny: A Precipitating Factor for Alzheimer’s Disease—An Insight on Repurposing Diabetes Pharmacological Treatments in Alzheimer’s Disease

Abstract

Background: The brain, through the sensory action of neurons situated in the hypothalamus and brainstem, plays a pivotal role in the homeostatic regulation of glucose metabolism. The brain senses changes in nutrients and hormones. It triggers negative feedback responses such as stimulating pancreatic insulin secretion, hepatic glucose production, and glucose/fatty acid metabolism in adipose tissue and skeletal muscle, and cellular glucose uptake, to restore glucose homeostasis. When glucose homeostasis is not tightly regulated, hyperglycemia may manifest, leading to diabetes mellitus (DM) and, in some cases, trickling into Alzheimer’s disease (AD). Purpose: This review article aims to establish the link between DM and AD by describing the processes from the onset of glucose dysregulation to the resulting changes in the brain that trigger AD symptoms. Furthermore, this review provides an understanding of interlinked processes, and proposes the repurposing of DM drugs as candidates for AD. Materials and Methods: Literature search was conducted using search engines such as PubMed and Google scholar, with papers written in English were selected. Results: Repurposing DM treatment towards AD is a promising area of research due to their pathogenically common features, which include metabolic dysfunction, insulin resistance, and inflammatory processes. This review highlights various diabetes treatments that could be possible molecular targets for AD treatment. Drugs such as glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, and intranasal insulin delivery are being explored and have shown potential for improving outcomes in AD. Through this exercise, we envisage that drug candidates and existing drug targets could be realized, most especially for AD, where optimal treatment is still a challenge. Conclusion: This article further summarizes a few DM treatment strategies that could be further investigated as drug targets to improve disease outcomes for AD patients.