Significance: It is of common sense that the world population is aging and life expectancy is increasing. However, as the population ages, there is also an exponential risk to live into the ages where the brain-related frailties and neurodegenerative diseases develop. Hand in hand with those events, the world is witnessing a major upsurge in diabetes diagnostics. Remarkably, all of this seems to be narrowly related, and clinical and research communities highlight for the upcoming threat that it will represent for the present and future generations. Recent Advances: It is of utmost importance to clarify the influence of diabetes-related metabolic features on brain health and the mechanisms underlying the increased likelihood of developing neurodegenerative diseases, in particular Alzheimer's disease. Thereupon, a wealth of evidence suggests that mitochondria and associated oxidative stress are at the root of the link between diabetes and co-occurring disorders in the brain. Critical Issues: The scientific community has been challenged with constant failures of clinical trials raising major issues in the advance of the therapeutic field to fight chronic diseases epidemics. Thus, a change of paradigms is urgently needed. Future Directions: It has become urgent to identify new and solid candidates able to clinically reproduce the positive outcomes obtained in preclinical studies. On this basis, strategies settled to counteract diabetes-induced neurodegeneration encompassing mitochondrial dysfunction, redox status imbalance, and/or insulin dysregulation seem worth to follow. Hopefully, ongoing innovative research based on reliable experimental tools will soon bring the desired answers allowing pharmaceutical industry to apply such knowledge to human medicine.
Keywords: Alzheimer's disease; brain; diabetes; mitochondria; redox imbalance; therapeutic approaches.