Project Summary
Alzheimer’s disease (AD) is the most common cause of age-related dementia, yet an effective and long-lasting treatment still does not exist. Recent studies indicate that transplanting neural stem cells can improve brain dysfunction in certain neurological disorders, but surprisingly has not yet been evaluated in AD. Our preliminary data show that neural stem cells rescue cognitive deficits in our animal models of AD and neurodegeneration. Remarkably, the mechanism underlying the improved cognition involves production of a neurotrophin, which are a family of proteins that induce and support the survival, development and overall function of neurons. In particular, our studies point to “brain-derived neurotrophic factor” (BDNF) as the key mediator of the benefits produced by the neural stem cells. Hence, the questions we are addressing are unique, as they will inform us whether neural stem cell transplantation offers a viable approach to treating AD or whether BDNF alone is better. A better understanding of the mechanism(s) by which stem cell transplantation improves cognitive function would undoubtedly lead to the identification of novel and more clinically applicable pharmacological approaches to treat the cognitive dysfunction. There are two specific aims that will occur: 1. Aim 1 will determine whether BDNF is sufficient to restore cognition in a mouse model of neurodegeneration. 2. Aim 2 will determine if BDNF is necessary to restore cognition. 3. Aim 3 will determine if the benefits of stem cells can be extended or improved by also selectively degrading the plaque protein, amyloid beta. Accumulation of amyloid beta is a hallmark of Alzheimer’s disease, and is the target of several drug discovery efforts.