Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-766 [PMID: 34168725 DOI: 10.4239/wjd.v12.i6.745]
Corresponding Author of This Article
Juan Salazar, MD, Doctor, Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, 20th Avenue, Maracaibo 4004, Venezuela. juanjsv18@hotmail.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Jun 15, 2021; 12(6): 745-766 Published online Jun 15, 2021. doi: 10.4239/wjd.v12.i6.745
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links
Milagros Rojas, Mervin Chávez-Castillo, Jordan Bautista, Ángel Ortega, Manuel Nava, Juan Salazar, Edgar Díaz-Camargo, Oscar Medina, Joselyn Rojas-Quintero, Valmore Bermúdez
Milagros Rojas, Mervin Chávez-Castillo, Jordan Bautista, Ángel Ortega, Manuel Nava, Juan Salazar, Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
Edgar Díaz-Camargo, Oscar Medina, Universidad Simón Bolívar, Facultad de Ciencias Jurídicas y Sociales, Cúcuta 540006, Colombia
Joselyn Rojas-Quintero, Pulmonary and Critical Care Medicine Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, United States
Valmore Bermúdez, Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla 080001, Colombia
Author contributions: Rojas M, Chávez-Castillo M and Bautista J conceived of the idea of the study and determined its general focus; Rojas M, Chávez-Castillo M, Bautista J, Ortega Á and Nava M contributed to the literature and wrote and revised the manuscript; Rojas M, Chávez-Castillo M, Salazar J, Bermúdez V, Díaz-Camargo E, Medina O and Rojas-Quintero J contributed to the review study and corrected the manuscript; all authors reviewed and approved the final version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Juan Salazar, MD, Doctor, Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, 20th Avenue, Maracaibo 4004, Venezuela. juanjsv18@hotmail.com
Received: February 13, 2021 Peer-review started: February 13, 2021 First decision: March 16, 2021 Revised: March 20, 2021 Accepted: May 21, 2021 Article in press: May 21, 2021 Published online: June 15, 2021
Abstract
At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.
Core Tip: Alzheimer’s disease and type 2 diabetes mellitus are highly prevalent chronic diseases that have shown a significant association. Important pathways have shown to be involved in this relationship, including the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, among others. This has led to the development of therapeutic approaches that can overlap and address both diseases. Some of the most promising interventions include the use of azeliragon, amylin, and glucagon-like peptide-1.
