UTHSC’s Liao Receives $2.6 Million Grant to Study Link Between Metabolic Syndromes and Dementia

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Dr. Liao (center), and her lab group received $2.6 Million to study the link between metabolic syndromes and dementia (Pictured from left to right: Xingyong Chen, MD, PhD; medical student Taiane Ferrari, Wei Zheng, MD, PhD; Tomi Akinduro, MD; graduate assistant Yi Zheng; graduate research assistant Mahesh Chandra Kodali; and Lubin Lan, MD, PhD) (Photo by Connor Bran/UTHSC)

According to the Alzheimer’s Association, an estimated 5.7 million Americans of all ages are living with Alzheimer’s dementia in 2018. While Alzheimer’s disease accounts for 60 to 80 percent of cases, vascular dementia is the second most common dementia type. Francesca-Fang Liao, PhD, professor in the Department of Pharmacology at the University of Tennessee Health Science Center, has been awarded over $2.6 million to study the mechanisms by which metabolic syndromes, such as high blood pressure or excess body fat, could increase one’s risk of dementia.

“There is increasing evidence that small vessel disease contributes, up to 40 percent, to cognitive impairment in the absence of clinical stroke and that subclinical small vessel disease drives cognitive changes, even when neuroimaging is normal,” Dr. Liao said. “Therefore, there is a pressing need to better understand the underlying mechanisms and identify preclinical biomarkers, as well as prevention and treatment strategies.”

Often incorrectly referred to as “senility” or “senile dementia,” which reflects a belief that serious mental decline is a normal part of aging, dementia is not a specific disease. Rather, dementia is an overall term that describes a group of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person’s ability to perform everyday activities. There is an increasing body of evidence that suggests inflammatory injury in the brain leads to neurological changes and could be linked to an increased risk of cognitive impairment or dementia. Dr. Liao’s lab has shown that certain small molecular modulators, specifically miRNA-21, possibly play a regulatory role in the brain.

“We speculate that blood-born factors, especially metabolic inflammatory factors, can cause harmful metabolic conditions in the brain via small secretory vesicles named ‘exosomes,’ ” Dr. Liao said. “Our lab hypothesizes that elevated miRNA-21 plays essential roles in the pathogenesis of aging and neurodegeneration. Therefore, eliminating miRNA-21 elevation will systemically prevent neurodegeneration.”

Dr. Liao’s lab also speculates that elevated circulating miR-21 contributes to neuroinflammation, neurological dysfunction, and neurodegeneration. Thus, these circulating processes may affect cell pathogenesis and the dissemination of inflammatory diseases, as well as serve as biomarkers and therapeutic-delivering cargos. “The long-term goal is to identify the molecular mechanisms underlying the increased risk for dementia patients with metabolic syndromes, and to develop new preventive and therapeutic strategies,” Dr. Liao said.

Her project titled, “Novel mechanistic link between metabolic changes and dementia – potential role of miRNAs,” is funded for five years.