Editors' ChoiceGastric Bypass Surgery

Bypassing Alzheimer’s Disease

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Science Translational Medicine  02 May 2012:
Vol. 4, Issue 132, pp. 132ec79
DOI: 10.1126/scitranslmed.3004207

Gastric bypass surgery improves the health of morbidly obese patients, who enjoy sustained weight loss, improved glucose metabolism, and amelioration of other obesity-related problems. Reduced risk of Alzheimer’s disease (AD) may be another benefit to add to this list. Ghanim et al. have recently reported that Roux-en-Y gastric bypass surgery can reduce the expression of AD-related genes in blood.

The authors performed Roux-en-Y gastric bypass surgery on 15 adult diabetic subjects with an average body mass index (BMI) of 52.1. Six months later, the patients’ average BMI had fallen to 40.4, and they showed significant decreases in blood glucose, serum insulin, and glycosylated hemoglobin levels. Because obesity and type 2 diabetes are risk factors for AD, the investigators speculated that this type of gastric bypass surgery might affect the pathogenesis and treatment of AD. They focused on peripheral blood cells that express amyloid precursor protein (APP), the protein that gives rise to the pathognomonic amyloid plaques in the brains of patients with AD. APP mRNA and protein levels were significantly reduced. Expression of other AD-related genes such as presenilin-2, clusterin, and PICALM was also lower in these blood cells after surgery. The procedure also reduced expression of the proinflammatory mediators that are usually associated with deteriorated glucose metabolism in obesity. Because gastric bypass surgery improves glucose metabolism, it has been assumed to also reduce the risk for AD in the long term. But now, this new work may have uncovered a marker of decreased risk for AD directly after surgery, giving us a clue about the connection between obesity and AD.

H. Ghanim et al., Reduction in inflammation and the expression of amyloid precursor protein and other proteins related to Alzheimer's disease following gastric bypass surgery. J. Clin. Endocrinol. Metab. 16 April 2012 (10.1210/jc.2011-3284). [Abstract]

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