2023 Alzheimer's Association Research Grant (AARG)
Local synaptic protein biogenesis in tauopathy
How does tau affect protein production in nerve cell connections?
Joongkyu Park, Ph.D.
Wayne State University
Detroit, MI - United States
Background
One of the major brain changes associated with Alzheimer’s is the accumulation of tau tangles. Tau is a protein that normally functions to transport nutrients and help nerve cells maintain their proper structure. In Alzheimer’s and other neurodegenerative diseases, tau protein can become modified or “misfolded” and can contribute to nerve cell death. Nerve cells in the brain connect and communicate to each other through specialized structures called synapses. Synapses are important for overall brain health, and for the creation and maintenance of memories.
Ribosomes are protein complexes found in all cells in the body, and their main function is to create new proteins. Recent studies have shown that new protein production in synapses regulates memory formation in the brain. However, how tau affects new protein production in synapses in Alzheimer’s is still unclear.
Research Plan
Dr. Joongkyu Park and colleagues aim to study the role of tau in protein production in synapses. Initial studies have shown that protein production is required for memory formation using genetically engineered mice with a molecular switch that can turn protein production on and off in synapses. To further their studies, they will use genetically engineered mice containing either regular or Alzheimer’s-associated tau protein. They will first isolate the synapses from the mouse brain, and measure differences in total protein levels and ribosomal proteins in the Alzheimer’s mice compared to regular mice. They will also test if tau affects the ribosomes by isolating synapses from mice and using advanced chemistry techniques to measure the types of ribosomes found in regular mice compared to Alzheimer’s mice.
Impact
The results of these studies will determine if tau affects memory function by preventing new protein production in synapses, and possibly lead to new interventions for the prevention of memory decline.