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2007 Grant - Gouras
Mechanism of Beta-Amyloid-Induced Synaptic Dysfunction
Gunnar K. Gouras, M.D.
Weill Medical College of Cornell University
New York, New York
Candidate for 2007 Zenith Fellows Award
Beta-amyloid is a protein fragment suspected of disrupting cell-to-cell communication and damaging nerve cells in persons with Alzheimer's disease. Traditionally, beta-amyloid is thought to accumulate outside of cells, where it forms amyloid plaques that are characteristic of the disease. Gunnar K. Gouras, M.D., has observed that beta-amyloid also accumulates inside of nerve cells in patients with Alzheimer's disease, as well as some persons with Down syndrome.
Dr. Gouras has observed that beta-amyloid accumulates in specific compart-ments inside the nerve cells known as endosomes. Endosomes are thought
to play important roles in synaptic transmission, the chemical and electrical process by which nerve cells communicate and process information.
Dr. Gouras and colleagues plan to study how accumulation of beta-amyloid within nerve cell endosomes affects synaptic transmission, potentially
causing or contributing to the synaptic dysfunction that is characteristic of Alzheimer's disease. The researchers plan to continue experiments already underway examining beta-amyloid in cultured nerve cells from mice that have been genetically altered to express Alzheimer-like pathology. They have already shown that these mice exhibit many of the abnormal properties of synaptic transmission seen in animal models of Alzheimer's disease. Future studies will explore how intracellular beta-amyloid accumulation in endosomes leads to neuronal dysfunction.
These studies may help to clarify the role of beta-amyloid in causing nerve cell dysfunction. Such an understanding is a first step toward identifying target molecules for treatment of Alzheimer's disease.