Could Alzheimer’s Disease be a Maladaptation of an Evolutionary Survival Pathway Mediated by Intracerebral Fructose and Uric Acid Metabolism?

As we continue to review the massive amount of literature available regarding insulin resistance and the fact that this is a precursor process for so many other diseases; the new buzz is the link to Alzheimer’s disease.  This review article theorizes a potential “protective mechanism” as one’s body is convinced that given the increases in fructose ingestion there must be famine, so fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism in attempts preserve glucose supply for the brain.  This idea may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation. This pathway can be engaged in multiple ways, including diets high in sugar, high glycemic carbohydrates, and salt. In summary, we propose that Alzheimer’s disease may be the consequence of a maladaptation to an evolutionary-based survival pathway and what had served to enhance survival acutely becomes injurious when engaged for extensive periods. 

Johnson, R.J, et. al.  2023.  The American Journal of Clinical Nutrition. 
 https://doi.org/10.1016/j.ajcnut.2023.01.002