BIOE Seminar: Chris Schaffer

Friday, May 10, 2019
9:00 a.m.-10:00 a.m.
A. James Clark Hall, Room 2132
Dr. Giuliano Scarcelli
scarc@umd.edu

Dr. Chris Schaffer
Associate Professor
Meinig School of Biomedical Engineering
Cornell University

Unexpectedly stalled: In vivo imaging reveals subtle cerebrovascular deficits in Alzheimer’s disease mouse models that underlie reduced cortical perfusion and contribute to impaired cognitive function


It has been clear for decades that blood flow to the brain is reduced by about one third in patients with Alzheimer’s disease. This decreased brain blood flow likely contributes to the cognitive decline in Alzheimer’s and may accelerate progression of the disease by impairing clearance of amyloid-beta. The mechanism causing this decreased brain blood flow, however, has not been elucidated. Using high-resolution in vivo imaging of blood flow in mouse models of Alzheimer’s disease, we have identified the plugging of capillary segments by firmly adhered white blood cells as a mechanism that contributes to this blood flow decrease. In Alzheimer’s mice, nearly 2% of capillaries have stalled blood flow due to an adhered neutrophil, while wild type mice have such stalls in less than 0.5% of capillaries. Because one stalled capillary decreases blood flow in many downstream branches, the 2% of capillaries stalled in the Alzheimer’s mouse models leads to substantial blood flow decreases. When we blocked leukocyte adhesion with antibodies against the neutrophil-specific protein Ly6G, cortical blood flow increased by ~20%. This increase in brain blood flow was accompanied by an immediate improvement in cognitive performance of mice on spatial and working memory tasks that brought performance up to that of control animals. This rapid improvement in cognitive function was observed across a range of animal ages, from animals just beginning to show cognitive impairment to animals with extensive Alzheimer’s-like neuropathology. These data suggest that white blood cells sticking in capillaries may be responsible for the reduced blood flow to the brain seen in Alzheimer’s patients and that treating this could both improve cognitive function and slow disease progression. This finding illustrates that significant physiological deficits can emerge from relatively subtle cellular interactions and that careful, in vivo studies provide one approach to dissecting such mechanisms.

About the Speaker

Chris B. Schaffer is an Associate Professor in the Meinig School of Biomedical Engineering and the Associate Dean of Faculty at Cornell University. Chris received his undergraduate degree from the University of Florida and his PhD from Harvard University, both in physics, before working as a post-doc in David Kleinfeld’s neuroscience laboratory at the University of California, San Diego. The lab he now jointly runs with Prof. Nozomi Nishimura at Cornell develops advanced optical techniques that enable quantitative imaging and targeted manipulation of individual cells in the central nervous system of rodents and uses such tools to construct a microscopic-scale understanding of normal and disease-state physiological processes in the brain. One area of current focus is understanding the role of brain blood flow disruptions in the development of Alzheimer’s disease. Chris is also active in developing novel educational strategies to teach science as a dynamic process for discovery that are used in outreach settings in middle and high-school science classes as well as in college-level courses. Chris also has a strong interest in science policy and spent a year in Washington, DC as a science policy fellow in the office of Senator Edward Markey. He continues to be active in policy, including through a science policy course he teaches. Chris is an accomplished surfer, having ridden waves all over the world and surfed some “big wave” spots, including greater than 20 ft. waves at Todos Santos, Mexico.

Audience: Public 

 

June 2019

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