|Volume 6 Issue 300 Published - 14:00 UTC 08:00 EST 26-Oct-2004 Next Update - 14:00 UTC 08:00 EST 27-Oct-2004||Editor: Susan K. Boyer, RN
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Researchers identify brain protein that halts progression of Alzheimer's
Researchers have identified a protein in the brain that halts the progression of Alzheimer's disease in human brain tissue. The protein, known as "transthyretin," protects brain cells from gradual deterioration by blocking another toxic protein that contributes to the disease process.
The National Institute of Environmental Health Sciences, a component of the National Institutes of Health, provided $1.25 million to University of Wisconsin-Madison scientists for the transthyretin study. The scientists will present their findings October 26 at the 34th annual meeting of the Society for Neuroscience in San Diego, Calif.
"The results of this study are promising," said Kenneth Olden, Ph.D., director of the NIEHS. "More studies are needed to understand how transthyretin can be used in treating Alzheimer's patients."
Alzheimer's disease progresses when a toxic protein, known as "beta-amyloid," attacks the brain's nerve cells involved in learning and memory. The beta-amyloid creates sticky plaques and tangles that gradually disable nerve cells, producing memory loss. Transthyretin appears to protect brain cells by intercepting the beta-amyloid and preventing it from interacting with the brain tissue.
"Based on the results of animal studies, we know that the disease process depends in large part on the delicate balance between the 'good' transthyretin protein and the 'bad' beta-amyloid protein," says Dr. Jeff Johnson, associate professor at the University of Wisconsin's School of Pharmacy and lead author on the study. "In Alzheimer's patients, the 'bad' proteins significantly outnumber the 'good' proteins."
Johnson discovered the effect of transthyretin while studying mice genetically engineered with defective genes taken from human patients with early-onset Alzheimer's disease. As expected, the defective genes produced mice with higher-than-normal levels of the toxic beta-amyloid protein. These mice did not, however, exhibit symptoms of Alzheimer's disease.
"We have a mouse whose brain is bathing in toxic beta-amyloid without exhibiting disease symptoms," says Johnson. "We were all asking the same question – Why aren't these nerve cells dying?"
Dr. Thor Stein, a researcher in Johnson's laboratory and first author of the study, then analyzed the brains of mice and noticed that the levels of transthyretin had increased dramatically. When Stein treated the mouse brain with an antibody that prevented transthyretin from reacting with the beta-amyloid protein, the mice showed brain cell death. "We concluded that the transthyretin must have protected the brain cells from the toxic effects of the beta-amyloid," says Johnson.
Test tube studies with cultured brain cells from human cortex support the findings. When Stein treated human brain cells with the transthyretin protein, then exposed the cells to the toxic beta-amyloid, the brain cell death was minimal. "Now that we have demonstrated that this protective mechanism is relevant to humans, we can start to identify strategies to slow nerve degeneration in Alzheimer's patients," says Johnson.
According to Johnson, this would involve developing drugs that would boost the transthyretin within the brain or methods depositing transthyretin into the brain. "Hopefully this research will inspire a new approach to the treatment of Alzheimer's, one focused on preventing the loss of the brain cells instead of treating the resulting symptoms."
Johnson foresees a time when family members with a genetic predisposition to Alzheimer's disease could take a yet-undeveloped drug to increase transthyretin protein and prevent the disease from developing. Theoretically, the drug also could be given in the early stages of Alzheimer's to stop progression of the disease, preserving a higher level of cognitive function in patients.
The transthyretin discovery will likely impact the screening of environmental chemicals for their potential role in causing or exacerbating Alzheimer's disease. "Researchers could develop tests that determine whether a particular chemical or agent in the environment is able to shift the delicate balance between the 'good' and 'bad' proteins," notes Johnson. "This would allow scientists to establish definitive links between environmental exposures and Alzheimer's disease pathology."
Additional Vidyya Resources:
Alzheimer's Disease And Dementia: Reminyl (Galantamine Hydrobromide)
Alzheimer's Disease Fact Sheet
Alzheimer's disease genetics fact sheet
Alzheimer's disease - Unraveling the mystery
Forgetfulness: It’s Not Always What You Think
Alzheimer's Disease: Unraveling the Mystery
New Fronts in Alzheimer's Research
Alzheimer's Disease Info: Questions to Ask the Doctor (Administration on Aging)
Mild Cognitive Impairment: Possible Predictor of Alzheimer's (Mayo Foundation for Medical Education and Research)
Agitation and Alzheimer's Disease (Alzheimer's Association) - Links to PDF File
Depression and Alzheimer's Disease (American Academy of Family Physicians)
Sleep Changes in Alzheimer's Disease (Alzheimer's Association) - Links to PDF File
Alzheimer's Disease Medications (National Institute on Aging)
Coping with Changes in Daily Life (Alzheimer's Association)
Helping Your Family and Friends (Alzheimer's Association)
Making Job Decisions (Alzheimer's Association)
Aluminum and Alzheimer's Disease (Alzheimer's Association) - Links to PDF File
Choosing Health Care Providers and Facilities (Alzheimer's Association)
Financial Matters for Alzheimer's Care (Alzheimer's Association)
Alzheimer's Disease Education and Referral (ADEAR) Center (National Institute on Aging)
Administration on Aging
Fisher Center for Alzheimer's Research Foundation
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Information from the FDA: Alzheimer's --- Searching for a cure -22-July-2003
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