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Weight Loss after Gastric Bypass Surgery
reduces expression of Alzheimer’s Genes
Newswise, June 13, 2011— Obesity is a risk
factor for Alzheimer’s disease, but weight
loss due to bariatric surgery may reduce the
risk of this common dementia, a new study
suggests. The results were at The Endocrine
Society’s 93rd Annual Meeting in Boston.
“Our 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,” said
the study’s main author, Paresh Dandona, MD,
PhD, professor at State University of New
York (SUNY) at Buffalo.
Past research has shown that obesity and
Type 2 diabetes increase the chance of
getting Alzheimer’s disease. In this study,
15 morbidly obese patients with Type 2
diabetes had Roux-en-Y gastric bypass
surgery and lost nearly 86 pounds, on
average, over six months. The patients gave
blood samples before surgery and six months
later.
Dandona and co-workers recently found that
white blood cells in the circulating blood,
called peripheral blood mononuclear cells,
express amyloid precursor protein.
This APP is the precursor of beta-amyloid,
protein pieces that form plaques in the
brain, one of the key brain abnormalities in
Alzheimer’s disease.
In this study, the researchers measured the
expression of APP, and it fell by 22 percent
after weight loss. Expression of the
messenger RNA that carries genetic
information for APP decreased by an average
of 31 percent, the data showed.
After weight loss there also was reduced
expression in other genes related to risk of
Alzheimer’s disease, according to the
authors. They included the presenilin-2
gene, which mediates the conversion of APP
into beta-amyloid. Also reduced in
expression was the gene for an enzyme known
as glycogen synthase kinase-3-beta
(GSK-3-beta), which phosphorylates, or
abnormally modifies, tau protein to form the
neurofibrillary tangles in the brains of
people with Alzheimer’s disease. Tangles are
a main suspect in the death of nerve cells
in this disease.
Dandona said that their clinical study
cannot prove that these effects are also
occurring in the brain. If it is true, he
said, “this may have implications for the
treatment of Alzheimer’s disease.”
“It is relevant that cognitive function has
previously been shown to improve with weight
loss following bariatric surgery,” Dandona
said.
Also, inflammation is another brain
abnormality seen in Alzheimer’s disease, and
in this study, the gene expression changes
paralleled the reductions in the blood of
mediators of inflammation, he said.
Funding for this study came from the
National Institutes of Health and the
American Diabetes Association. The genetic
testing for APP is not yet commercially
available, Dandona said.
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