Cognitive impairment and AD: targeting presynaptic therapeutic mechanisms
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abstract
Nerve cells communicate with one another by sending neurotransmitters (or chemical messengers) through specialized regions called synapses that connect one nerve cell to another. Cellular communication is necessary to support memory and other cognitive functions. In Alzheimer’s disease synapses become damaged which may contribute to impaired nerve cell communication and declines in cognitive function. Because synaptic damage occurs early in the disease process, scientists are working to understand the underlying mechanisms so that targeted treatments can be developed. In previous studies, Karienn Montgomery, Ph.D., and colleagues found that aging rats with memory problems show a disruption in the normal balance of neurotransmitters needed for synaptic function in the brain. This disruption may lead to synaptic damage and cognitive decline, but the underlying mechanisms are not yet clear. Research Plan For their current studies, Dr. Montgomery and colleagues plan to expand their earlier findings using genetically engineered “optogenetic” mice in which researchers can use pulses of light to regulate the activity of nerve cell synapses. The researchers will study both male and female mice of different ages to determine if there are sex-related differences in synaptic function across the lifespan. They plan to identify the molecules involved in both the normal and abnormal function of nerve cell synapses. The researchers will also begin testing potential drug candidates that may be able to help restore synapse function. Impact The results of these studies could provide new information on how nerve cell communication is disrupted in Alzheimer’s disease, and how these mechanisms may differ between males and females. Ultimately, such knowledge could lead to the development of novel therapies to preserve synapses and potentially slow or halt the progression of Alzheimer’s disease.
