Blood Brain Barrier and Metabolism in Aging and AD

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.

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.