Providence (R.I.) Journal, January 11, 2008

NEW LEAD DANGER FOUND

[Rachel's introduction: "...every monkey exposed to lead in the study had an accumulation of plaque on their brains similar to what occurs in people who suffer from Alzheimer's."]

By Peter B. Lord, Journal Environment Writer

A scientific team headed by a researcher at the University of Rhode Island has found a link between early exposure to lead in the environment and the onset of Alzheimer's disease in old age.

The link was discovered by feeding lead to baby monkeys and then studying their brains 23 years later. Monkeys don't get Alzheimer's disease, but every monkey exposed to lead in the study had an accumulation of plaque on their brains similar to what occurs in people who suffer from Alzheimer's.

Nasser Zawia, a pharmacy professor at URI, said he thinks his work is significant because it is the first time scientists have shown links between lead and Alzheimer's in primates. He has done similar research showing links involving mice and rats.

Zawia and a spokesman for the national Alzheimer's Association cautioned that the study should not prompt lead-poisoning victims or their families to fear that their lead exposure will automatically lead to Alzheimer's.

Until the last few years, Rhode Island has been a hot bed of lead poisoning. More than 30,000 children have been diagnosed with elevated lead levels since 1991.

"I would say it's just another factor, another risk factor," Zawia said in a telephone interview. "It's like how smoking is a risk factor for cancer. It puts you at greater risk. But there are 100 other things that can intervene between early life and old age. And this does not just apply to lead. Certain other things may lay dormant for many years."

William H. Thies, vice president of medical and scientific relations at the Alzheimer's Association in Chicago, called the study "good, solid basic science," but he also emphasized "making a leap from this paper to saying Alzheimer's disease is caused by early childhood lead exposures doesn't fit."

Thies recalled that in the past some people pinpointed aluminum as a cause of Alzheimer's and many people threw away their aluminum pots and pans before that theory was rejected.

"I predict we'll find no single, monolithic cause," said Thies. "We know there are already lots of good reasons for removing lead from the environment. And it's certainly possible lead is a contributor to Alzheimer's. But I don't think it's the answer to solving Alzheimer's."

Thies also observed that while lead has been sharply reduced in the U.S. environment in recent decades by taking it out of paints and gasoline, the incidence of Alzheimer's continues to grow in epidemic proportions.

Some 5 million people are afflicted now, according to the association, and some experts predict there may be 16 million victims by 2050. Some fear Alzheimer's could bankrupt the Medicare budget.

Zawia has studied the neurological effects of lead and other metals for eight years, using some $700,000 in grants from the National Institutes of Health.

But he said it was a rare, serendipitous find several years ago when he learned that other researchers were working with a small group of monkeys to determine the effect of lead poisoning on their intelligence -- research that had nothing to do with Zawia's work with Alzheimer's and other diseases.

The researchers worked with two small groups of monkeys, exposing one to lead for 400 days and keeping the other group lead-free. The amount of lead exposure was designed to mimic the levels children are often exposed to. The monkeys were turned over to a National Institutes of Health facility in North Carolina where they lived for 23 years.

In 2003, the monkeys were put to death and their tissues examined.

The initial research was done by Deborah C. Rice, now a toxicologist at the Maine Environmental Protection Agency. Zawia said he learned about it from Dr. Jean Harry, one of his mentors at the National Institutes of Health.

Zawia and his researchers were able to obtain samples and do complex analyses of protein and plaque development.

They found that the lead exposures at a young age reprogram the way genes express themselves during the individuals' lives. Specific genes became more active and created the proteins that make the peptides that create the plaque, said Zawia.

Zawia says he hopes the next step will be to obtain financing to do more research with human populations.

He says his is part of a growing body of work that looks at how various toxins such as lead and pesticides, when applied to very young people, lead to diseases much later in life.

"It's a new way of looking at public health," Zawia said. "What happens in early life does not mean it's a done deal. There may be consequences later. It's a new way of looking at disease."

Thies said Zawia and his group should be recognized for the good biochemistry work they did and he believes their work will become a part of the science that leads to treatments for Alzheimer's.

The study was published Jan. 2 by the Journal of Neuroscience, a premier publication in its field.

The research was completed by scientists from URI's Department of Biomedical and Pharmaceutical Sciences, the Department of Biomedical and Pharmaceutical Science at the University of Montana, the National Institutes of Health, the Maine Department of Health and Human Services, and the Laboratory for Molecular Neurogenetics at Indiana University School of Medicine.

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