The link between diabetes mellitus and Alzheimer’s disease

Abstract

Introduction. Type 2 Diabetes mellitus (T2DM) represents a major public health burden and a growing prevalent chronic disease around the world. It is known that more than 425 million people have diabetes, and this number is expected to rise to over 642 million by 2040. Alzheimer’s disease (AD) is the main cause of dementia, affecting over 26 million people worldwide, and its prevalence continues to increase. Both conditions are related to age, and in the last decades, an interesting link between them has appeared from various studies that affirm that individuals with T2DM are 2–4 times more likely to develop AD, but definitive biochemical mechanisms remain unknown. Aim of the study. This review has the intention to present that type 2 diabetes mellitus (T2DM) is a significant risk factor for cognitive dysfunction or dementia, especially those related to Alzheimer's disease Materials and methods. For the study were used electronic medical platforms such as PubMed Databases, Hinary and other scientific libraries like Google Scholar. It have been selected and analyzed 40 articles including manuscripts, reviews, and publications for the last 10 years. Results. Of the multiple intersection between T2DM and AD, the most pronounced is the insulin resistance, characterized by hyperinsulinemia and hyperglycaemia. Insulin resistance decreases glucose metabolism which in turn hyperphosphorylates tau protein causing neurofibrillary tangles. In AD, the extracellular accumulation of Aβ plaques, intracellular aggregation of hyperphosphorylated tau protein in neurofibrillary tangles (NFTs), and neuronal loss occur in the cortex and hippocampus, where are located insulin-dependent receptor GLUT 4 and insulin-independent receptors GLUT1 and GLUT3. Receptors are affected by the abnormal glucose metabolism, and not only, including enzymes like GSK-3, Cdk-5, CK-1 and others. The mechanism of influence does not stop here; hyperglycemia can activate K-ATP channels that increase cellular excitability and leads to an elevated ISF Aβ. Moreover, insulin alteration in diabetes can interrupt brain cholesterol metabolism leading to metabolic dysfunction. Conclusions. T2DM and AD were earlier considered as two independent metabolic disorders. However, the present study has clearly stated the presence of common pathophysiological and epidemiological mechanisms, together with signaling pathways that associates a relation between these two pathologies. It might be possible that therapeutics for T2DM would be effective for AD, but in order to prove that, more investigations are needed. Recently, AD has been called Type 3 Diabetes.