Acarbose ameliorates western diet‐induced metabolic and cognitive impairments in the 3xTg mouse model of Alzheimer’s disease

Abstract

AbstractBackgroundMany age‐related diseases are major risk factors of Alzheimer’s disease (AD), such as type II diabetes mellitus and cardiovascular disease. As such, there is a growing body of interest in determining if already in use geroprotective interventions for these disorders may also be beneficial in AD. One such intervention is acarbose, an anti‐diabetic drug that improves glucose homeostasis, reduces risk of myocardial infarction, and extends lifespan in various mouse models.MethodWe administered either a western diet or a western diet containing acarbose to diet‐induced obese male and female 3xTg mice starting at 6 months of age. Over the following 6 months, we examined a number of facets of metabolic health and analyzed cognitive function using Barnes maze. After sacrificing mice at 12 months of age, we analyzed aspects of AD pathology in the brain using Western blotting and immunohistochemistry.ResultBoth male and female 3xTg mice treated with acarbose exhibited decreased body weight and adiposity despite increased food consumption. Acarbose‐treated mice also had an overall improvement in glycemic control and increased energy expenditure. Female mice showed dramatic improvements in cognition and AD pathology, and males exhibited minor improvements as well. Preliminary data also suggest that there is increased gliosis in mice fed a western diet, which may be ameliorated by acarbose.ConclusionIn the context of a western diet, acarbose has dramatic benefits on metabolic health, cognitive health, and AD pathology. This suggests that there is potential for already in use geroprotective pharmaceuticals such as acarbose to ameliorate AD pathology.