A protein called transthyretin has been identified that protects human neurons from Alzheimer's disease-related damage through blockage of the protein beta-amyloid, according to a presentation at the annual meeting of the Society for Neuroscience.

"The results of this study are promising," said Kenneth Olden, PhD, of the National Institutes of Health. "More studies are needed to understand how transthyretin can
be used in treating Alzheimer's patients."

Beta-amyloid creates sticky plaques and tangles in the brains of Alzheimer's disease patients that gradually disable neurons, producing memory loss. Transthyretin appears to intercept beta-amyloid in some manner that prevents it from interacting with neurons.

"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," said Jeff Johnson, PhD, a study coauthor. "In Alzheimer's patients, the 'bad' proteins significantly outnumber the 'good' proteins."

Johnson discovered the effect of transthyretin while studying mice that had been 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 beta-amyloid. However, the mice did not exhibit symptoms of Alzheimer's disease.

"We have a mouse whose brain is bathing in toxic beta-amyloid without
exhibiting disease symptoms," said Johnson. "We were all asking the same question -- Why aren't these nerve cells dying?"

Dr. Thor Stein, lead author of the study, analyzed mouse 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 beta-amyloid, the mice demonstrated brain cell death.

"We concluded that the transthyretin must have protected the brain cells from the toxic effects of the beta-amyloid," said Johnson.

Test tube studies with cultured brain cells from human cortex supported the findings. When Stein treated human brain cells with the transthyretin protein, then exposed the cells to the toxic beta-amyloid, neuron loss 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," said Johnson.

According to Johnson, this would involve developing drugs that would boost the transthyretin level within the brain or methods that would deposit 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 is likely to have an impact on 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," noted Johnson. "This would allow scientists to establish definitive links between environmental exposures and Alzheimer's disease pathology."