Husband & Wife Duo Combating Dementia Through Neurological Research

Dr. Vivian Nguyen and husband Dr. Kristian Doyle of The University of Arizona. 

Photo credit: Dr. Vivian Nguyen.

SelectScience^® spoke with Dr. Vivian Nguyen, an Assistant Professor in the Department of Neurology at The University of Arizona. Dr. Nguyen works in close collaboration with her husband Dr. Kristian Doyle, whom she met while at Stanford University. Her research looks at mixed dementia, a condition in which the pathological characteristics of more than one type of dementia exists in a patient. Read on to find out how this husband and wife duo work in tandem at the forefront of neurology.

SS: What are your main research interests?

VN: We hope to untangle causality in mixed dementia, and from there we hope to develop treatments.

To investigate post-stroke dementia, my husband’s work is centered on understanding why inflammation lasts for months following stroke; why there is chronic blood-brain barrier dysfunction following stroke; and whether stroke causes long-term dysfunction of the glymphatic system.

My research is then centered on determining the impact of each of these three things on the development of Alzheimer’s disease like neuropathology, and hence determining the contributors of mixed dementia.

SS: What circumstances led to you becoming an expert in the field of mixed dementia research?

VN: In graduate school and during my postdoctoral training, I primarily focused on Alzheimer’s disease related research. However, during my time as a Senior Staff Scientist at Stanford University, I helped my husband, Dr. Kristian Doyle, a stroke expert, to develop a model of post-stroke dementia. Because of the prevalence of Alzheimer’s disease and other dementias, for which there are no cures, and the devastation they have wrought in my own family, my personal goal has always been to advance the development of dementia therapeutics. With expertise in both Alzheimer’s and post-stroke dementia, it was natural for me to converge the two and develop my research program in the field of mixed dementia.

SS: What have been your most interesting findings and how do they affect the broader scientific field?

VN: During his post-doctoral fellowship with Dr. Marion Buckwalter at Stanford University, my husband and Dr. Buckwalter were the first to show that in the mouse brain, inflammation persists for months following stroke and can contribute to the development of a dementia-like phenotype¹. Following on from this work, I recently published a paper² that provides the most comprehensive characterization to date of the inflammatory response to stroke in the human brain. This paper demonstrates that there is also a persistent inflammatory response in the human brain following stroke.

With our research, we are hoping to bring more scientific attention to the fact that inflammation following stroke is very slow to fully resolve. Our data suggests that not only is this itself neurotoxic, it also has important consequences for the blood-brain barrier and the glymphatic system. We are testing the hypothesis that it is a cause of post-stroke dementia in some patients, and mixed dementia in other patients, such as those at risk of developing Alzheimer’s disease.

SS: What do you think are the future goals and directions for your research field and what technologies do you think will be important?

VN: Our research is highlighting the fact that the inflammatory response to stroke does not appear to resolve as effectively as it does in other tissues following ischemia. We believe this lack of resolution has long-term consequences for the development of post-stroke dementia and mixed dementia, and is likely to occur to a different extent in different individuals. To date, most stroke research in rodent models and human studies has focused on the acute response to stroke.

Therefore, an important future goal is to determine how variable the inflammatory response to stroke is in different people, and how it is impacted by age-related co-morbidities. The future technology that is important for achieving this goal is the development of more sensitive and precise PET and MRI-based imaging modalities for detecting and monitoring the long-term sequelae of stroke, such as inflammation.

SS: Do you think you and Kristian will continue to collaborate?

VN: Absolutely. Kristian’s stroke expertise adds to my Alzheimer’s disease expertise. In light of the fact that the average age of stroke sufferers is 67, and over 90% of Alzheimer’s disease patients are over the age of 65, combining our research expertise rather than investigating each disease separately is very important. Most previous research on dementia has focused on a single disease, and little is known about how they impact each other. We hope to work together to fill this gap in knowledge.

SS: And finally, what are the main technologies you use?

The main methodologies we use are immunostaining, confocal microscopy, electron microscopy, histology, flow cytometry, multiplex immunoassays and mouse behavioral testing. We used MilliporeSigma cytokine/chemokine kits to determine the characteristics of the cytokine and chemokine response to stroke in both mice and human brain tissue. We found that MilliporeSigma provided more comprehensive immunology panels for both mouse and human tissue compared to their competitors. The kits have always worked well and the inclusion of quality controls within each kit means that we can easily authenticate and validate that they’ve worked well.

Learn more about the technology utilized in Dr. Nguyen’s research, in this recent article.

References:

1. Doyle, K., Quach, L., Solé, M., Axtell, R., Nguyen, T., Soler-Llavina, G., Jurado, S., Han, J., Steinman, L., Longo, F., Schneider, J., Malenka, R. and Buckwalter (2015) ‘B-lymphocyte-mediated delayed cognitive impairment following stroke’, The Journal of neuroscience : the official journal of the Society for Neuroscience., 35(5), pp. 2133–45.

2. Nguyen, T., Frye, J., Zbesko, J., Stepanovic, K., Hayes, M., Urzua, A., Serrano, G., Beach, T. and Doyle, K. (2016) ‘Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue’, Acta neuropathologica communications., 4(1).