Looking for answers on how to keep older brains healthy

Ridding the brain of harmful beta-amyloid plaques is a common target for new therapies.

By Susan J. Landers — Posted Sept. 11, 2006

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Researchers are pursuing numerous leads in their quest for the secrets of a healthy, aging brain.

One recent study focuses on the genes that allow us to reach age 90 with robust mental faculties. Another opens the door to new drug treatments that sweep out toxic bits of protein that build up in the brains of people with Alzheimer's disease. A third homes in on the dangers posed by high-fat, copper-rich diets.

The role of exercise and the wear and tear of stress on the brain also are being explored, and Swedish researchers even have assembled a risk predictor for dementia that weighs low education, advanced age, hypertension, cholesterol levels and obesity.

If any of these promising projects reach fruition, the yield in terms of public health benefits would be enormous as thousands of baby boomers approach the age at which diseases such as Alzheimer's take an increasing toll. Advanced age is the greatest risk factor for this illness, with one in 10 people older than 65 and nearly half of those 85 and older affected, according to the Alzheimer's Assn.

Research in the healthy aging field has exploded as attempts are made to uncover the cause of such puzzling maladies as Alzheimer's, Parkinson's or Huntington's disease. "We have extremely well-trained physicians who are seeing patients all the time and are bringing data back to scientists," said Andrew Dillin, PhD, assistant professor at the Salk Molecular and Cell Biology Laboratory, in LaJolla, Calif. Since the cause of these diseases is unknown, "we really have to throw everything at it," he said. "It's a huge field with a lot of different approaches coming out of it."

Dr. Dillin, working with researchers at Scripps Research Institute in LaJolla, unveiled new findings in the Aug. 10 Science Express, the online version of Science, that could lead to the development of drugs to prevent build-up of harmful beta-amyloid.

Their research also found that the aging process impedes two molecular clean-up crews from getting rid of the toxic aggregates of this protein fragment. Although beta-amyloid production occurs in all brains, healthy cells clear away excess amounts. The brains of people with Alzheimer's can't control this build-up, and scientists have struggled for years to find out why.

To determine whether aging or simply time's passage was the culprit, Dr. Dillin, working with Scripps chemistry professor Jeffery Kelly, PhD, experimented with roundworms that were engineered to age at different rates. Roundworms can produce human beta-amyloids in their body wall muscles. The scientists then postulated: If it just takes time to accumulate the harmful protein fragments, then the roundworms designed to live for 25 days and those that live for 50 days should evidence the onset of disease at the same time. But that didn't happen. The roundworms treated to live longer managed to do so successfully, while those who lived a normal 25 days exhibited an incapacitating build up of beta-amyloid aggregates.

"Our study revealed that the age onset of these diseases is not simply a matter of time but that the aging process plays an active role in controlling the onset of toxicity," Dr. Dillin said. The researchers also found that cells use an unexpected two-pronged strategy to rid themselves of harmful aggregates, thus opening the way to new drug targets.

Meanwhile, Martha Clare Morris, ScD, associate professor of medicine at Rush University Medical Center in Chicago, zeroed in on diet to determine why there is an increased rate of cognitive decline among older people.

She found that people who consume high amounts of food with saturated and trans fats and have a higher intake of copper may show a decline in thinking, learning and memory abilities -- signs of Alzheimer's. Her findings were published in the August Archives of Neurology.

Plus, it seemed to take both the high fats and the copper to produce the result. "In people who did not have a high-fat diet, there was no association of the copper cognitive decline," she said.

While copper is an essential nutrient, fats are not, she said. "This is another reason that a diet high in saturated and trans fat tends to cause problems."

Previous studies also have shown that copper can cause the harmful amyloid plaques to form.

Based on this research, a focus in Alzheimer's research has been to find medications that can mimic the action of the healthy brain and clear out these dangerous plaques, said Sam Gandy, MD, PhD, chair of the Alzheimer's Assn.'s medical and scientific advisory council. "That's the most popular hypothesis of how Alzheimer's begins."

In July, the 10th International Conference on Alzheimer's Disease and Related Disorders was held in Madrid and attended by 5,000 researchers and clinicians. A similar meeting in 1988 attracted 500 attendees.

But the sad part is that funding is being cut, Dr. Gandy said. "Just as we are bringing medicine into the clinic, we are being knee-capped by losing the support we need to keep it going."

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Dementia risk

Swedish researchers examined data on 1,409 people who were examined in midlife and again 20 years later to gather a set of predictors for the development of dementia. The findings highlight the importance of vascular factors and could help identify people who might benefit from intensive lifestyle changes and pharmacological treatments.

Future dementia was associated with:

  • Advanced age
  • Low education levels
  • Hypertension
  • Hypercholesterolemia
  • Obesity

Source: The Lancet Neurology, Aug. 3 (online)

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External links

"Experimental Alzheimer drugs targeting beta-amyloid and the 'amyloid hypothesis' " Alzheimer's Assn. fact sheet, in pdf (link)

"Opposing Activities Protect Against Age Onset Proteotoxicity," abstract, Science Express, published online Aug. 10 (link)

"Dietary Copper and High Saturated and Trans Fat Intakes Associated with Cognitive Decline," abstract, Archives of Neurology, August (link)

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