Significant Weight Loss from Bariatric Surgery May Reduce Alzheimers Risk

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Researchers have found that obesity can increase the risk of Alzheimer’s disease by as much as 80%. Co-morbid conditions that obesity causes, such as diabetes, high blood pressure, and heart disease add to the risk by damaging blood vessels and increasing the chances of vascular dementia. A new study has found that the significant weight loss that follows bariatric surgeries such as Roux-en-Y gastric bypass can decrease the risk of dementia by reducing the expression of certain genes.

Alzheimer’s disease is the fourth leading cause of death in the United States. It is characterized by neuronal cell death and a progressive loss of functioning in the brain. Both obesity and type 2 diabetes can increase the risk of developing the disease by increasing the risk of inflammation in the brain leading to increased brain levels of beta-amyloid.

Weight Loss and Normalization of Blood Sugar Can Decrease Inflammation and APP Gene Expression

Paresh Dandona MD PhD, a professor at State University of New York (SUNY) at Buffalo, and colleagues followed 15 morbidly obese patients with Type 2 diabetes who underwent Roux-en-Y gastric bypass surgery. The participants lost an average of 86 pounds each over the course of six months. Subjects gave blood samples at the beginning of the study as a baseline and again at the end for comparison.

The researchers measured the expression of amyloid precursor protein or APP, a protein that is implicated in the formation of plaques in the brain which is a key characteristic of Alzheimer’s disease. APP balance is also critical for normal neuronal development, connection of synapses, and dendritic spine development, all of which have implications in the cognitive decline seen in Alzheimer’s.

Read: Obesity Linked to Risk of Alzheimer's Disease

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After weight loss, the expression of APP decreased by 22%. Expression of the messenger RNA that carries the genetic information for APP also decreased by an average of 31%.

The researchers also found a reduction in the expression of other genes which are related to Alzheimer’s risk including the presenilin-2 gene which mediates the conversion of APP into beta-amyloid. Another gene, glycogen synthase kinase-3-beta (or GSK-3-beta) was also reduced. This gene abnormally modifies tau protein to form the neurofibrillary tangles in the brains of people with Alzheimer’s which ultimately leads to death of nerve cells.

Mediators of inflammation, another brain abnormality seen in Alzheimer’s patients, were also reduced.

Read: Excess Belly Fat Raises Risk of Alzheimer's and Other Dementias

The authors conclude that “obesity and caloric intake modulate the expression of APP in MNCs.” While the research only measured blood changes and cannot prove that the effects are also occurring in the brain, they write, “If indeed this effect also occurs in the brain, this may have implications for the pathogenesis and the treatment of Alzheimer's disease."

The results from this study will be presented at The Endocrine Society’s 93rd Annual Meeting in Boston.

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