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2014 Grants - Wesson
Impact of Upstream Neurodegeneration on Downstream Cortical Function
Daniel Wesson, Ph.D.
Case Western Reserve University
2014 New Investigator Research Grant
Alzheimer’s disease is a progressive disorder, starting in certain areas and proceeding through the brain in a particular pattern. Specific brain regions may develop Alzheimer’s-like changes including the clumping of a protein fragment called beta-amyloid, ultimately forming amyloid plaques, a hallmark of the disease. Though amyloid clumping can first occur in certain brain areas, it appears to trigger more widespread damage to the brain’s circuitry — the pathways through which chemical and electrical signals are transmitted and brain areas are connected. Thus damage in the “upstream” brain areas hinders the ability of connected “downstream” brain areas from processing information correctly. This can lead to a loss of function related to the networks affected, for example sensory networks such as those needed for olfaction which is the sense of smell.
Daniel Wesson, Ph.D., and colleagues plan to study how damage localized to cells in the nasal cavity behind the nose (called olfactory receptor neurons, or ORNs) may lead to Alzheimer’s-like changes in the brain. When odor molecules enter the nose, ORNs send electrical signals to a specific structure in the brain called the olfactory bulb, where they are processed as smells. People with Alzheimer’s disease often suffer damage to the olfactory system, and loss of smell is a common feature of the disease. Dr. Wesson’s team hopes to learn how damage to “upstream” ORNs can alter “downstream” circuitry throughout the olfactory system.
For this effort, the researchers will use genetically-engineered mice that have elevated levels of beta-amyloid in their ORNs and experience changes in their olfactory behavior. Dr. Wesson and colleagues will assess whether ORN damage related to amyloid clumping hinders the electrical signaling in other parts of the animals’ olfactory system. They will then determine whether these changes lead to loss in the rodents’ ability to detect odors or possibly effect cognition. Collectively, the study’s results could refine our understanding of how olfactory system damage relates to the progression of Alzheimer’s disease and could possible lead to the development of tests to identify an individual at the earliest dates of Alzheimer’s disease.