Obesity and type 2 diabetes can increase the risk of Alzheimer’s disease. Research in animal models has shown that dietary interventions like calorie or protein restriction can improve metabolic health as well as slow or prevent Alzheimer’s disease. However, these types of interventions are hard to sustain in the long-term. This led Assistant Professor of Minimally Invasive Surgery Dave Harris, MD to the question of whether and how weight loss (bariatric) surgery would affect Alzheimer’s disease risk. With a new two-year, $311,000 research grant from the National Institute on Aging, he and his team in the Wisconsin Surgical Laboratory in Metabolism (WiSLiM) will be examining this very question.
“Sleeve gastrectomy, which is the most performed type of bariatric surgery, has a profoundly positive impact on obesity, metabolic disease, and end organ health, and it can extend life by as much as 10 years. In small studies, it has also been shown to improve cognition, increase grey and white matter in the brain, and reduce the circulating amyloid precursor proteins that are characteristic of Alzheimer’s disease,” explained Harris. “But while we have a growing body of evidence on the gut-brain connection and about the benefits of sleeve gastrectomy to treat or prevent Alzheimer’s disease, we don’t understand exactly how or why it has this effect.”
The WiSLiM team plans to perform sleeve gastrectomy on obese mice that have been fed a high fat, high sugar Western diet. They will then conduct a series of tests to look at how the surgery affects frailty and cognition in the mice, and examine how it affects the physiology of the brain at a molecular level. They will also analyze how it impacts the interaction of a variety of factors that affect metabolism (e.g., genetics, gut microbial health, diet, and other lifestyle/environmental factors), known as the metabolic phenotype.
“This study will add to our understanding of how altering the gut can in turn alter brain health. We hope to reveal novel targets for the future treatment of devastating dementia-related diseases like Alzheimer’s,” said Harris.