After watching his grandmother mentally and physically deteriorate from dementia, Jee Hoon Roh, MD, PhD, decided as a medical student that he would work to help others like his grandmother, as well as reduce the burden on their caregivers.
DR. JEE HOON ROH...Image Tools
Dr. Roh attended medical school at Korea University and completed his neurology residency at the Korea University Medical Center in Seoul Korea. In 2009, he also received his PhD in neuroscience from Korea University. Currently, he is a postdoctoral fellow associate at Washington University in St. Louis, MO.
Dr. Roh will use his AAN Clinical Research Training Fellowship to observe the sleep-wake cycle in humans and mice as a diagnostic and therapeutic target in the study of Alzheimer disease (AD). Neurology Today spoke with Dr. Roh about his interest in human cognition and how he hopes to make strides in AD research.
WHAT WAS YOUR RESEARCH QUESTION?
We want to investigate whether impaired sleep affects the aggregation of amyloid beta (Abeta) peptide in the brains of humans and in mouse models of Alzheimer disease.
In mouse and human brains, levels of Abeta increase while they are awake and decrease during sleep (this is known as diurnal fluctuation) prior to Abeta aggregation. The amount of sleep decreases with age in both humans and mouse models of AD. My hypothesis for this study is that individuals who show reduced sleep time and poorer sleep quality will also show accelerated AD-type brain changes.
TELL US MORE ABOUT YOUR METHODOLOGY.
In order to determine whether reduced sleep time might affect Abeta aggregation, I first found that diurnal fluctuation of Abeta occurs normally in all regions in the brains of young mice prior to Abeta aggregation with a normal sleep-wake cycle. I then discovered that the diurnal fluctuation of Abeta is disrupted during aging with reduced sleep time, which may lead to Abeta accumulation in aged mice.
In order to understand the mechanism underlying these findings, I will investigate whether Abeta pathology is decreased by modulating specific genes that increase the amount of sleep in aged mice. I will also study whether reducing Abeta pathology in the brain helps maintain the normal diurnal fluctuation of Abeta as well as the normal sleep-wake cycle in aged mice. I will examine whether the amount and quality of sleep early in life is relevant to the development of Abeta accumulation in the human brain.
WHY DID YOU CHOOSE THIS SPECIFIC PROBLEM?
AD is the most common cause of dementia, and the pathology begins to develop when the Abeta peptide aggregates in the brain. Since this aggregation begins about 10 to 15 years before the clinical onset of AD, early intervention to prevent the aggregation of Abeta is likely to be important in preventing AD. I focused on sleep as a diagnostic and therapeutic target, which can be modulated well before the Abeta aggregation.
If I find that Alzheimer disease brain changes and the deterioration of sleep-wake cycle are improved through specific treatment interventions and genetic manipulation of sleep in animals and if results from human sleep studies support this notion, this will provide insight into how early manipulation of the sleep-wake cycle may impact the development of AD.
DO YOU HAVE A RESEARCH MENTOR?
I really appreciate the strong support from my mentor, Dr. David M. Holtzman. Every interaction with Dave at the bench as well as in the hospital has greatly inspired me. He is clearly my role model. I am also very grateful for the mentorship from Dr. John C. Morris.
WHY DID YOU CHOOSE TO GO INTO NEUROLOGY?
I initially became interested in neurology because of my grandmother. She raised me for more than 20 years and suffered from vascular dementia for 10 years before passing away. As the disease progressed, she had difficulty communicating and became emotionally labile. As a medical student, I became frustrated that I could no longer have a reasonable conversation with the person to whom I had grown so close. Since then, I have had a strong interest in human cognition and dementia. Specifically, I am interested in disease-modifying treatment of dementia to relieve the burden on patients and their families. There are still lots of questions that remain unanswered in the field, and I'm excited for the future.
AAN Clinical Research Training Fellowships are funded by the AAN, the AAN Foundation, and the AAN Foundation Corporate Roundtable, and provide $55,000 per year for two years, plus $10,000 per year for tuition to support formal education in clinical research methodology at the fellow's institution or elsewhere. Fourteen fellowships were awarded for 2011, and more than 70 training fellowships have been awarded through the program since its inception in 1996. For more information about the program, visit http://bit.ly/egrG8L.