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2011 Grants - Yang
Synaptic Pathology Underlying Memory Loss in a Mouse Model of Alzheimer's Disease
Guang Yang, Ph.D.
New York University School of Medicine
New York, New York
2011 New Investigator Research Grant
Synapses are tiny channels in the brain though which neurons send and receive chemical messages. Healthy synapses are often characterized as having high plasticity, or the ability to change the strength of their chemical signals. Synaptic plasticity probably facilitates learning and memory within the brain. In early Alzheimer's disease, the plasticity of synapses becomes altered, leading to memory deficits later in the disease course. Yet scientists know little about how synaptic changes may cause learning and memory problems.
For this study, Guang Yang, Ph.D., and colleagues will conduct two experiments with mice to learn more about the biological processes that link synaptic loss and cognitive decline. First, they will use a sophisticated imaging technique to examine the brains of mice engineered to develop Alzheimer's-like symptoms. Previous research suggests that the plasticity of synapses involved in motor skill learning may be associated with the maintenance of normal cognitive behaviors. The investigators will examine whether decreasing this learning-dependent plasticity in mice will result in behavioral impairments.
In addition, Dr. Yang's team will create another Alzheimer's mouse model in which mice lack a certain group of microglia in their brains. These particular immune system cells are thought to break down unwanted beta-amyloid, a protein fragment closely linked to Alzheimer's pathology or brain changes. The researchers expect to determine how eliminating such microglia may affect beta-amyloid production in the mice. They also hope to discover whether these mice suffer greater than normal losses of learning-associated plasticity and greater than normal behavioral deficits. Results of these efforts could shed new light on how cognitive decline occurs in Alzheimer's. Moreover, the microglia tested in the study could be identified as a possible therapeutic tool for treating dementia.