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Surgery-related weight loss may reduce dementia risk
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ENDO 2011
BOSTON — Patients who lose weight after undergoing Roux-en-Y gastric bypass surgery may also reduce their risk for Alzheimer’s disease, researchers found.
It is known that obese people and those with type 2 diabetes are at increased risk for developing Alzheimer’s disease. Paresh Dandona, MD, PhD, professor at the State University of New York at Buffalo, said this study “shows for the first time that weight loss resulting from bariatric surgery leads to a reduction in the expression of genes related to Alzheimer’s disease.”
The small study included 15 morbidly obese patients with type 2 diabetes. Researchers collected blood samples before surgery and 6 months after surgery. During the study period, patients lost an average of 86 lb and the average BMI decreased from 54.4 to 40.5.
Recently, Dandona and colleagues discovered that peripheral blood mononuclear cells express amyloid protein (APP), a precursor of beta-amyloid and a key abnormality in Alzheimer’s disease. In this study, they found that the expression of APP decreased 22% after 6 months of weight loss and expression of the messenger RNA that carries genetic information for APP decreased 31%.
Post-surgery weight loss was also associated with reduced expression in other genes related to risk for Alzheimer’s disease. Expression in the presenilin-2 gene (PN2), which mediates the conversion of APP into beta-amyloid, decreased 27%; and the glycogen synthase kinase-3-beta (GSK-3-beta) gene, which phosphorylates tau protein to form neurofibrillary tangles in the brain, decreased 28%. According to the researchers, these changes were parallel with other reductions in proinflammatory mediators such as C-reactive protein (from 10.7 mg/L to 5.8 mg/L).
“We conclude that obesity and caloric intake modulate the expression of APP and other Alzheimer’s disease-related genes in mononuclear cells,” the researchers wrote in the study abstract. “If indeed this effect also occurs in the brain this may have implications for the pathogenesis and the treatment of Alzheimer’s disease. It is relevant that cognitive function has been shown to improve with weight loss following bariatric surgery.”
Genetic testing for APP is not yet commercially available, Dandona said.
Disclosure: Dr. Dandona is a principal investigator for GlaxoSmithKline; a clinical researcher for Sanofi-Aventis; and a speaker for Novartis Pharmaceuticals, Eli Lilly & Company, GlaxoSmithKline and Sanofi-Aventis.
For more information:
- Dandona P. OR11-3. Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston.
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