Neurovascular Changes in Aging and Alzheimer Disease

Yi Su, PhD
Banner Health (Phoenix, AZ)

Collaborators

Tammie L.S. Benzinger, MD, PhD
Washington University School of Medicine (St. Louis, MO)
Andrei Vlassenko, MD
Washington University School of Medicine (St. Louis, MO)
Year Awarded:
2017
Grant Duration:
July 1, 2017 to June 30, 2021
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2017272S
Award Type:
Standard
Award Region:
US Northwestern
Yi Su, PhD

As a junior investigator, this award is an important step for me to develop an independent research program.

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Blood Brain Barrier and Metabolism in Aging and AD

Summary

Vascular contributions to Alzheimer’s disease (AD) and dementia are increasingly recognized, but the exact role of the neurovascular system, which supplies blood to the brain, remains unclear in AD and dementia. We hypothesize that changes to the neurovascular system underlie and contribute to the onset and progression of AD and dementia. In this project, we propose to use cutting-edge imaging techniques to measure these changes in vivo, and examine their relationship with aging and AD.

Details

The goal of this project is to use novel imaging techniques to examine change in brain metabolism and the loss of blood-brain barrier (BBB) integrity as a consequence of aging and AD.

Recent studies demonstrated that change of the neurovascular system is an important component of the many pathways in aging and AD that eventually lead to dementia. Specifically, we and others have detected evidence of BBB breakdown as in association with cognitive deficits. Using recently developed novel imaging techniques developed in our lab, we will measure BBB permeability in a memory and aging cohort and investigate whether BBB permeability increases in cognitively impaired participants compared with normal controls.

Another commonly adopted biomarker in AD research is the metabolic rate of the brain. The conventional approach measures brain metabolism as a ratio of target brain region to some reference region, while our preliminary study demonstrated that using a recently developed absolute measure of brain metabolism correlated better with cognitive performance. In this study, we further investigate the relationship between brain metabolism and other AD biomarkers using the quantitative methodology.

Finally, our research is built upon recently developed novel imaging techniques in our lab. In this project, we will acquire additional human imaging data to further validate and refine these imaging techniques to facilitate future adoptions of these techniques by our group as well as the general research communities.

In summary, our proposal uses cutting-edge imaging techniques to measure neurovascular system function in vivo. Specifically, by multi-modal analysis of positron emission tomography (PET) data and magnetic resonance (MR) imaging data acquired using several different MR sequences, we can measure BBB permeability, brain glucose metabolism, and glucose transporter activity. We then plan to examine the relationship of these physiological parameters to aging and cognitive impairment to better understand the role of cerebrovascular system function in AD and dementia. The success of this project will provide new tools to measure brain function and pathophysiology in vivo (ie, in the brains of living people), which may facilitate the development of interventional strategies and approaches to prevent and treat AD and dementia.

About the Researcher

Dr. Yi Su received his B.S. degree in chemistry from the University of Science and Technology of China and Ph.D. in biomedical engineering from Mayo Graduate School. During his post-doctoral training at Washington University in St. Louis, Dr. Su was further exposed to advanced preclinical and clinical multi-model imaging techniques. Dr. Su then became a faculty member in the Department of Radiology at Washington University School of Medicine and started his career investigating brain function in health and disease with a focus in AD research. Recently, Dr. Su developed several novel imaging techniques that enable quantitative measurement of brain function and pathophysiology in vivo, and he is currently exploring the application of these techniques in aging and AD research.

Personal Story

I received multidisciplinary training in math, physics, and biomedical engineering during my education. Currently, I am a junior faculty member in the Neuroimaging Laboratories at Washington University School of Medicine, and I am interested in the development of novel imaging techniques and the application of these techniques in the investigation of brain function in health and disease. With the rapid expansion of the elderly population of the world, neurological diseases in the aging population, especially AD, are becoming a major burden both economically and socially. My current research is focused on gaining a better understanding of AD pathogenesis through the use of cutting-edge imaging techniques, ultimately to facilitate the development of therapeutic approaches to prevent, delay and treat AD. As a junior investigator, I am very grateful for the BrightFocus Foundation and its donors for this award, which is an important step for me to develop an independent research program. Through this award, we will further refine and validate the imaging techniques we recently developed and gain more knowledge of the development, onset, and progression of AD pathologies that eventually lead to dementia. It will also provide additional data that are needed to secure long-term funding to support further investigations into the neurovascular aspects of AD and dementia.

Publications

Schultz SA, Gordon BA, Mishra S, Su Y, Morris JC, Ances BM, Duchek JM, Balota DA, Benzinger TLS. Association between personality and tau-PET binding in cognitively normal older adults. Brain Imaging Behav. 2019 Sep 5. doi: 10.1007/s11682-019-00163-y. [Epub ahead of print] PubMed PMID: 31486975 PubMed Icon Google Scholar Icon

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