UCF Researcher Examines Link Between a Protein and Alzheimer’s

A UCF medical researcher is examining how the deficiency of a specific protein in the brain can cause Alzheimer’s disease — a discovery that would open doors to better treatments and diagnostics.

The Ed and Ethel Moore Alzheimer’s Disease Research Program, which aims to improve the health of Floridians by researching treatments for Alzheimer’s, recently awarded Jihe Zhao $350,000 to better understand the molecular changes that cause the disease. Alzheimer’s affects some 6 million Americans including about 600,000 Floridians.

Zhao, a cancer researcher at the Burnett School of Biomedical Sciences, has focused much of his research into developing new targets for effective anticancer therapy and has now expanded his research to include Alzheimer’s disease.

Historically, Alzheimer’s research has focused on plaques and tangles of proteins that form in the brain cells of Alzheimer’s patients. And much of that work has focused on reducing these blockages. However, therapies based on reducing plaque have not been effective.

Zhao is taking a different approach, investigating the molecular causes of changes in the brain that lead to Alzheimer’s.

“Identifying the molecular causes and mechanisms behind the disease is the first step to developing effective therapies,” he said.  His research will focus on KLF8 (Kruppel-like factor 8) — a protein important for brain function that has been recorded as deficient in patients with Alzheimer’s. “But how this deficiency contributes to the development of Alzheimer’s disease has never before been investigated due to the lack of proper animal models,” Zhao says. “So this is the very first study of its kind.”

Zhao’s lab has developed novel mouse models in which the amount of KLF8 protein in neurons can be altered to see how reduced levels impact the brain and development of Alzheimer’s. He says preliminary evidence shows a KLF8 deficiency causes neurons to die and that changes in the protein impact genes critical for maintaining cognitive function and a normal brain environment.

“These results strongly suggest that KLF8 plays a role in protecting neurons and that loss of KLF8 function may be a molecular cause of Alzheimer’s disease,” Zhao says, adding that the findings of this study will be critical to advancing knowledge of how Alzheimer’s develops and provide new targets for therapy.

The study could also open doors for earlier diagnosis and possible prevention of the disease.

In the U.S. alone, the annual cost of providing care to Alzheimer’s patients was estimated at $320 billion in 2022 and this number is expected to increase if more effective therapies are not discovered.

“So it is urgent to better understand the disease mechanisms so we can diagnose it earlier and create more effective treatment to save lives and reduce the burden on the nation’s healthcare,” Zhao says.

Zhao received his MD at the Chinese Medical University and a Ph.D. at Tohoku University (Japan). He completed postdoctoral training at Cornell University.