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2008 Grants - Tuszynski
Therapeutic Effects of BDNF in APP Mutant Mice
Mark Tuszynski, M.D., Ph.D.
University of California, San Diego
La Jolla, California
2008 Investigator-Initiated Research Grant
Alzheimer's disease, especially in its early phases, is characterized by selective neurodegeneration in specific regions of the brain. One of the regions most severely affected is known as the entorhinal cortex. Indeed, neurodegeneration in the entorhinal cortex may explain the specific loss of short-term memory in persons with early Alzheimer's disease.
Mark Tuszynski, M.D., Ph.D. and colleagues have found that a natural substance in the brain, brain-derived neurotrophic factor (BDNF), prevents nerve cell death in the entorhinal cortex of rats. BDNF also boosts the function of nerve cells in this region of the brain. The researchers have also characterized some of the mechanisms by which BDNF affects nerve cells in the entorhinal cortex.
Dr. Tuszynski and colleagues have begun to study how BDNF affects learning and memory, as well as the function of the entorhinal cortex in mice that have been genetically altered to overexpress amyloid precursor protein (APP). Such overexpression of APP causes these mice to exhibit traits of Alzheimer's disease that resemble those seen in humans with the disease.
The researchers plan to use genetic methods to increase expression of BDNF in the brains of these Alzheimer-like mice. They will then examine whether BDNF protects the entorhinal cortex from degradation, and whether brain function is preserved as a consequence. These studies will answer important questions about the mechanisms of neurodegeneration in early Alzheimer's disease, and they may suggest strategies for slowing or halting progression of the disease.