UTHSC researchers awarded $1.9 million to study white matter mechanisms underlying dementia

The National Institute of Neurological Disorders and Stroke has awarded two UTHSC researchers over $1.9 million to study the pathogenesis of white matter damage, a main contributing factor to dementia. Francesca-Fang Liao, PhD, and Fu-Ming Zhou, PhD, both professors in the Department of Pharmacology, Addiction Science, and Toxicology, are co-investigators on the project titled "Blood-brain-barrier and white matter mechanisms underlying dementia."

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. Dr. Liao has spent over five years studying specific molecular and cellular events that cause insufficient blood flow to the brain. Based on previous findings, Dr. Liao hypothesizes that degeneration of the brain's capillary mural cells is the earliest pathological event in white matter disease, preceding blood-brain-barrier breakdown and neocortical neurodegeneration. Her findings point to a specific protein, pericyte-BMP4, as a critical initiating factor.

Dr. Liao's team will conduct microscopic tissue imaging of small vessels controlling brain blood flow to determine when and where pericyte losses happen. The team will also profile BMP4 changes in different cell types and verify BMP4 protein upregulation in white matter pericytes using human brain cortical samples from vascular dementia cases. Finally, Dr. Liao's lab will analyze RNA sequencing data on isolated micro vessels to identify new potential targets for treating white matter disease.

Dr. Zhou, who has spent two decades studying Parkinson's disease, will work from the physiological angle, examining nerve conduction and impaired neurotransmitter release in animal models. His findings may provide neurophysiological evidence for what causes vascular changes in white matter, problems in the cerebral cortex, and functional loss in neurodegenerative diseases.

"Dr. Liao is a visionary scientist on vascular dementia and Alzheimer's disease," Dr. Zhou said. "I am delighted that we are combining our expertise and skills to investigate some difficult, but important, questions about the pathogenesis of vascular dementia and Alzheimer's disease."

"Vascular dementia is the second most common form of dementia after Alzheimer's disease," said Dr. Liao. "With Dr. Zhou joining in force, we are embarking on a new research path to underpin early molecular and cellular mechanisms distinctive for and also shared by these two major types of dementia."