Receptor Critical in Neurodegeneration Reduces Alzheimer's Plaque

Increasing the level of a protein that plays a key role in traumatic spinal cord injuries and multiple sclerosis reduces the concentration of disease-causing plaque in Alzheimer’s disease, Yale School of Medicine researchers report in the Journal of Neuroscience.

“Our new findings indicate that pharmacological methods to increase the protein, NogoReceptor, may be a way to treat the deficits associated with Alzheimer’s disease,” said Stephen Strittmatter, M.D., senior author of the study and co-director of the new program in Cellular Neuroscience, Neurodegeneration and Repair at Yale.

It is well known that the clinical dementia of Alzheimer’s disease is associated with specific pathological changes in the brain. One such change is deposits of the peptide beta-amyloid in brain plaques, a hallmark of the disease. Nerve fibers also play a crucial role in the neurodegenerative process of Alzheimer’s disease. “We asked whether those mechanisms that regulate nerve fiber growth might lessen the Alzheimer’s disease process,” said Strittmatter, professor in the Departments of Neurology and Neurobiology.

In brain sections from Alzheimer’s patients, the protein NogoReceptor is distributed in an unusual pattern in conjunction with beta-amyloid peptide, which is the primary component of plaque that forms in the brains of patients with Alzheimer’s disease, he said.

“Using genetic mouse models, we show that the NogoReceptor and beta-amyloid bind to one another,” Strittmatter said. “Therefore, we investigated whether the NogoReceptor might alter the Alzheimer’s process.”

“Using an Alzheimer’s model in mice, we demonstrated that decreasing the level of NogoReceptor causes more of the Alzheimer’s beta-amyloid to build up in the brain,” he said. “Conversely, higher levels of NogoReceptor reduced the concentration of the disease-causing beta-amyloid in the brain.”

Strittmatter’s laboratory previously determined that a molecular pathway involving the NogoReceptor protein played a crucial role in determining whether nerve fibers grow or remain stationary in the adult brain. The protein inhibits the regeneration of axonal nerve fibers in injured spinal cords and in neurodegenerative diseases such as multiple sclerosis.

Journal of Neuroscience (26) 5: 1386-1395 (February 1, 2006)

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