"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 p
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Contact: John Peterson
peterso4@niehs.nih.gov
919-541-7860
NIH/National Institute of Environmental Health Sciences
25-Oct-2004