Alzheimer's disease: Is there a relationship between brain renin-angiotensin system, estradiol and glucose transporter-4 (GLUT-4)?

One of the diseases more related to the continuous aging of the population is Alzheimer's disease, which is a type of dementia currently without either effective diagnosis biomarkers or treatments. Its higher prevalence in women makes it necessary to study pathways/systems that could participate and/or be involved in its development, as well as those that could be affected by hormonal factors, which, in this case, are estradiol levels. In this sense, one of the systems under study that is gaining special relevance in the scientific community is the brain renin-angiotensin system and its regulatory proteolytic enzymes. This system is strongly modulated by estrogens, and it is also connected with the cerebral glucose metabolism through the angiotensin IV receptor, also recognized as the insulin-regulated aminopeptidase (IRAP). Due to the fact that the cerebral glucose metabolism is highly compromised in patients with Alzheimer's disease, it is necessary to know the elements of the systems and their functions in this process, namely, the cerebral renin-angiotensin system, estradiol and IRAP, an enzyme and receptor co-localized in brain tissue with the insulin-dependent glucose transporter 4 (GLUT4). Knowledge of the connection between them could shed light on the molecular mechanisms of this disease and also provide new diagnostic and therapeutic targets.