APOE as a risk factor for Alzheimer’s disease and lipid metabolism disorders: molecular analysis

Abstract

The gene encoding apolipoprotein E (APOE) plays a key role in many biological processes, including lipid metabolism, brain homeostasis, and functioning of the circulatory system. APOE gene polymorphism is one of the most important risk factors in the context of Alzheimer’s disease (AD), which is the most common cause of dementia. Different variants of APOE alleles, particularly APOE ε4, are associated with an increased risk of AD and accelerated progression of this disease. Mechanisms by which APOE ε4 contributes to AD pathogenesis include amyloid metabolism disorders, tautopenias, immune system dysfunction, and functional abnormalities of the blood-brain barrier. The APOE gene may play an important role not only in the pathogenesis of AD, but also in the development of cardiovascular diseases, such as coronary heart disease, stroke and atherosclerosis. As in AD, different variants of APOE alleles may affect lipid metabolism, inflammation, vascular functions and the processes of apoptosis, which translates into an increased risk of diseases. The article presents the current state of knowledge about the role and importance of the APOE gene in the pathomechanism of AD and cardiovascular diseases. Understanding molecular mechanisms and gene-environment interactions associated with APOE may contribute to changes in the diagnostic process. The development and improvement of genetic tests may help in early detection and treatment of diseases, and even, in some cases, prevent their occurrence.