Jefferson scientists discover mechanism tying obesity to Alzheimer's disease

December 29, 2005

If heart disease and diabetes aren't bad enough, now comes another reason to watch your weight. According to a study just released, packing on too many pounds can increase the risk of developing Alzheimer's disease.

A team led by researchers at the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia and Edith Cowan University in Joondalup, Western Australia has shown that being extremely overweight or obese increases the likelihood of developing Alzheimer's. They found a strong correlation between body mass index and high levels of beta-amyloid, the sticky protein substance that builds up in the Alzheimer's brain and is thought to play a major role in destroying nerve cells and in cognitive and behavioral problems associated with the disease.

"We looked at the levels of beta-amyloid and found a relationship between obesity and circulating amyloid," says Sam E. Gandy, M.D., Ph.D., director of the Farber Institute for Neurosciences. "That's almost certainly why the risk for Alzheimer's is increased," says Dr. Gandy, who is also professor of neurology, and biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University. "Heightened levels of amyloid in the blood vessels and the brain indicate the start of the Alzheimer's process." The scientists reported their findings this month in the Journal of Alzheimer's Disease.

According to, Dr. Gandy, evidence has emerged over the last five years that many of the conditions that raise the risk for heart disease such as obesity, uncontrolled diabetes, hypertension and hypercholesterolemia also increase the risk for Alzheimer's. Yet exactly how such factors made an individual more likely to develop Alzheimer's remained a mystery.

Dr. Gandy, Ralph Martins, Ph.D., of Edith Cowan University and their colleagues measured body mass index and beta-amyloid levels in the blood. They also looked at several other factors associated with heart disease and diabetes, such as the inflammatory marker C-reactive protein, insulin, and high density lipoprotein in 18 healthy adults who were either extremely overweight or obese. They found a "statistically significant correlation" between body mass index and beta-amyloid.

"Ours is one of the first attempts to try to find out on both the pathological and the molecular levels how obesity was increasing the risk of Alzheimer's," says Dr. Gandy, who serves as chairman of the Alzheimer's Association's Medical and Scientific Advisory Council.

One implication of these findings could be that by losing excess weight and maintaining normal body weight, an individual might reduce the risk of developing Alzheimer's. However, this has not been proven, notes Dr. Gandy.

"What's especially interesting about this is that several studies are showing that even medical conditions in midlife may predispose to Alzheimer's later on," he says. "The baby boomers today should pay attention to this. Their medical risk factors today will play a role 30 years later. Think about weight, cholesterol, blood pressure, which could affect you long-term. In terms of Alzheimer's, another risk factor is maintaining an active mental lifestyle."

The next step is to follow such patients over the long term to see how many do indeed develop Alzheimer's. "We need to first develop a medicine that is effective in humans in lowering amyloid accumulation or generation," says Dr. Gandy. "We have those now in mice and we are testing them in humans. If we can develop such a medicine, then the question will be, if we can lower amyloid, will that in fact prevent Alzheimer's?"
-end-


Thomas Jefferson University

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