A Wayne State University School of Medicine faculty member has been awarded a total of $2.3 million by the National Institute on Aging of the National institutes of Health for two new, concurrent projects that both address questions related to Alzheimer’s disease, a progressive, age-related degenerative brain disease characterized by memory problems, impaired judgment, cognitive issues and changes in personality. 

Joongkyu Park, Ph.D., assistant professor of Pharmacology and of Neurology, is the principal investigator on “Local protein synthesis in tau pathology neurodegeneration,” a five-year, $1.9 million R01 research project that seeks to understand how tau pathology alters protein biogenesis in neuronal compartments. Brains with Alzheimer's disease, or AD, display the presence of increased protein accumulations, such as intracellular tau inclusions (neurofibrillary tangles) and extracellular beta-amyloid deposits (senile plaques). Dr. Park will test whether pathogenic forms of tau specifically interfere with dendritic protein synthesis and determine if the effect contributes to the pathologic features seen in Alzheimer’s disease.

The second grant, “Redirected CaMKII for restoring deficits in Alzheimer’s disease models,” is a two-year, $413,915 R21 exploratory/developmental project that aims to examine and understand how redirected calcium/calmodulin- dependent protein kinase II alpha improves neuronal dysfunctions and memory deficits in Alzheimer’s disease models.

“The most notable symptom is a significant cognitive impairment accompanying a substantial loss of dendritic spines and, eventually, neurons themselves. Since these end-stages are mostly irreversible, it is critical to identify appropriate molecular targets for intervention before the synaptic dysfunction and neuronal loss become permanent,” Dr. Park said.

Brains with AD display the presence of amyloid plaques and neurofibrillary tangles.

“However, alterations in synaptic structure, function and plasticity appear before these pathologies arise in various AD models, highlighting the pathological significance of early-stage synaptic alterations, potentially driven by AD-associated proteins, as a proximal event in AD etiology,” Dr. Park said. “Our lab focuses on local translation alteration (R01) and CaMKIIa mislocalization (R21) in the AD context. Using novel molecular approaches we developed recently, we will study how those mechanisms are altered in AD and how molecular understanding can be leveraged to mitigate or prevent pathologic features.”

The grants are based on previous work completed in the Park lab.

“I’m honored, humbled and excited to continue our research on synapse biology in the context of Alzheimer’s disease with these two new NIH grants,” he said.

“With Alzheimer’s disease on the rise, innovative research holds the key to unlocking hope and transforming care for millions affected,” said Ezemenari Obasi, Ph.D., vice president for research & innovation at Wayne State University. “These new NIH grants led by Dr. Park will provide an opportunity for important research to help develop new understandings of Alzheimer's disease and related dementias and possible therapeutic interventions that may one day change the lives of many.”

The grant numbers for these National Institute on Aging of the National Institutes of Health awards are R01AG089566 and R21AG083760.