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URI scientist awarded $499,863 in federal grants to examine lead exposure link to Alzheimer’s disease

Media Contact: Dave Lavallee, 401-874-5862

Work in College of Pharmacy to focus on early life exposures

KINGSTON, R.I. -- October 14, 2004 -- A University of Rhode Island biomedical scientist has found in a preliminary study a link between infant exposure to lead and precursors to Alzheimer’s disease.

Intrigued by the findings, the National Institute of Environmental Health Sciences, a branch of the National Institutes of Health, has awarded Nasser Zawia, URI associate professor of biomedical sciences in the College of Pharmacy, $499,863 in grants to expand his research.

“We want to examine the fetal basis for adult disease,” said Zawia, a resident of Warwick. “If you are exposed in-utero to a toxin while your brain is developing, could that lead to a compromised system that leads to later disease?”

Zawia and a team of graduate students examined the neurological effects of lead exposure on laboratory rats. One group was exposed in early life--three weeks old; another in old age—18 to 20 months, and another, the control group, had no exposure.

In humans, Alzheimer’s disease is a progressive neurodegenerative disorder, which is characterized by inflammation, cell loss, and amyloid plaques, which are protein fragments that accumulate between nerve cells (neurons) in the brain. These protein fragments are normally broken down and eliminated in a healthy brain, but with Alzheimer's, the fragments accumulate to form hard, insoluble plaques.

The researchers found that the rats exposed early in their lives showed a higher level of a precursor protein in their brains for Alzheimer’s. However, that precursor protein did not show up until old age. The rats exposed to lead in old age showed no effects from the exposure.

The precursor protein appears in those rats exposed in early life, but then they recover and the precursor is not present. It re-appears in those rats at 20 months, or old age. Furthermore, the transcription factor (an on-off switch that activates the gene) that regulates the expression of the gene that produces this protein follows a similar course.

“We found that lead does have an effect on the operator of the gene,” Zawia said. “The goal is to find environmental risk factors for such diseases as Alzheimer’s, Huntington’s and Parkinson’s.”

He said his team is focusing on lead because it is so prevalent in the environment and because it is the number one hazard for children, according to the federal Centers for Disease Control.

The team is also targeting Alzheimer’s and its potential relationship to environmental risk factors because most cases have no genetic component. He said about 95 percent of Alzheimer’s cases are not genetic. “If there is no inherited trait, then that could mean something in the environment is triggering it. There are potential toxins in the environment that promote the development of Alzheimer’s.

“If you are exposed in utero to lead while the brain is forming, it could lead to damage that would manifest itself later in life,” he said. “ In early childhood, the last set of neurons develops in the brain. Unlike other organs, brain cells cannot be replaced. Therefore damaged cells remain for the lifetime of an individual, and this damage may be masked during life, but reappear later. We call it silent damage.”

The Biomedical Research Infrastructure Network (BRIN) at URI and the federal government funded Zawia’s initial study.

The new $499,863 project will allow Zawia to expand his research to mice. With additional research funding in the future, Zawia plans to inject human genes into the mice’s brains to see if amyloid plaques develop after they are exposed to lead. “In the previous study we could only see the precursor proteins, not the plaques.

“No one in the world has done this type of research yet that looks at the fetal basis of adult disease. We want to answer the question, ‘Does early exposure to a heavy metal lead to Alzheimer’s disease’?”

The new study will also allow the researchers to expose mice fetuses to lead to see if there are even more dramatic effects later in life, Zawia said.
Zawia hopes that this research leads to prevention strategies. “We’re opening up a whole research field in the environmental impact on brain diseases,” he said.

Eventually, he said the work could lead to examinations of polychlorinated biphenyls (PCBs) and pesticides and their potential links to brain diseases.