Alıntı:Weight Loss After Gastric Bypass Surgery Reduces Expression of Alzheimer’s Genes

Released: 6/5/2011 8:00 AM EDT
Embargo expired: 6/5/2011 11:15 AM EDT
Source: Endocrine Society

Newswise — 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 will be presented Sunday 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.

Alıntı:June 17, 2011 — Results of a new study provide more evidence that diet may modulate the risk for Alzheimer's disease.

In a 4-week diet intervention study, healthy cognitively intact older adults who stuck to a low-saturated-fat, low-glycemic-index diet experienced decreases in cerebrospinal fluid (CSF) levels of β-amyloid 42, a biomarker of Alzheimer's disease risk.

But in a group of older adults with amnestic mild cognitive impairment (aMCI), the healthy diet had the opposite effect, raising CSF levels of this protein.

These observations "made sense to us," Suzanne Craft, PhD, of the Veterans Affairs Puget Sound Health Care System in Seattle, Washington, who worked on the study, told Medscape Medical News.


Dr. Suzanne Craft
"That's because in patients with Alzheimer's disease," she explained, "β-amyloid 42 sticks in the brain and so levels are lower in the CSF, and something that is going to reverse that process is going to raise levels in the spinal fluid."

"But for a healthy adult," she said, "it looks like levels get higher and higher over the course of life until, for some people, they reach a tipping point where [β-amyloid 42] begins to stick in the brain. In healthy adults, having levels decrease is actually a healthy pattern."

"It looks like a healthy diet that contains a lot of fruits and vegetables and healthy fats would be important for people who have Alzheimer's disease or conditions that put them at risk for developing Alzheimer's disease," Dr. Craft said.

The study appears in the June issue of the Archives of Neurology.

Mounting Evidence That Diet Matters to the Brain

There is a "fair amount" of evidence starting to accrue in the epidemiologic literature looking at what patterns of diet seem to both be protective and alternatively place someone at greater risk for Alzheimer's disease, Dr. Craft noted.

"That evidence," she said, "is suggesting that a diet like the Mediterranean diet seems to have a protective effect and a diet that has a lot of saturated fat and sugar seems to place you at greater risk."

"Those studies are very important for setting the stage, but what's different about our study is that we actually placed people on a very specific diet and provided every piece of food that they ate for an entire month," the researcher said.

The high-saturated-fat/high-glycemic-index diet included 45% fat (25% saturated fat), 35% to 40% carbohydrates (glycemic index > 70), and 15% to 20% protein. The low-saturated-fat/low-glycemic-index diet included 25% fat (< 7% saturated fat), 55% to 60% carbohydrates (glycemic index < 55), and 15% to 20% protein.

Participants included 20 healthy adults with a mean age of 69.3 years and 29 adults with aMCI and a mean age of 67.6 years. For 4 weeks, 24 participants followed the high-fat diet (9 healthy adults and 15 with aMCI) and 25 followed the low-fat diet (11 healthy adults and 14 with aMCI).

The number of times participants were nonadherent to their assigned diet was "small and comparable among groups," the authors note. The mean nonadherent incidents per week ranged from 1.23 to 1.80 per group.

Effects on β-amyloid "Striking"

As expected, in both groups, the high-fat diet produced unhealthy changes in serum cholesterol and insulin profiles, while the low-fat diet produced healthy changes in these measures.

Notably, the investigators say, the 4-week diet intervention had "striking effects" on β-amyloid 42 concentrations in CSF, the primary outcome measure, and the effects differed by diet and by cognitive status.

In the healthy adults, the high-fat diet increased CSF β-amyloid 42 levels, essentially moving them "in a direction that may characterize a presymptomatic stage of Alzheimer's disease before plaque deposition," the investigators note in their report. The high-fat diet also increased concentrations of the oxidative stress marker F2-isoprostane and lowered insulin levels.

Conversely, in the participants with aMCI, β-amyloid 42 levels were nearly unchanged by the high-fat diet, "possibly because more extreme intervention is needed to exacerbate already-extant pathologic processes," the investigators suggest.

The low-fat diet had beneficial effects in both the healthy participants and the participants with aMCI.

In the aMCI group, it increased β-amyloid 42 concentrations in the CSF, contrary to the pathologic pattern of lowered CSF β-amyloid 42 typically observed in Alzheimer's disease.

In the healthy adults, the healthy diet decreased CSF β-amyloid 42 levels, which may help move them away from the "tipping point" that corresponds with the start of β-amyloid brain deposition, leading eventually to cognitive impairment.

In both groups, the low-fat diet reduced F2-isoprostane concentrations; increased apolipoprotein E, which aids with β-amyloid clearance; and was associated with improved delayed memory, a hallmark cognitive deficit in aMCI and Alzheimer's disease.

In their paper, the researchers say their study provides "converging support" for recent epidemiologic investigations of dietary patterns and Alzheimer's disease risk.

The results, they conclude, support further investigation into the "possibility that consumption of a diet high in saturated fat and simple carbohydrates may contribute to pathologic processes in the brain that increase the risk of Alzheimer's disease, while a diet low in saturated fat and simple carbohydrates may offer protection against dementia and enhance brain health."

The study was supported by grants from the National Institute on Aging and by funding from the Nancy and Buster Alvord Endowment. The authors have no disclosed no relevant financial relationships.

Arch Neurol. 2011;68:743-752. Abstract