All Posts by Melissa Day

Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy

Vascular mechanisms of Alzheimer’s disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms of tau (tau oligomers) accumulate in brain microvasculature of AD and other tauopathies, including prominently in microvascular endothelial cells. Here we show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy and drives AD-like brain microvascular deficits. Microvascular impairments in P301S(PS19) mice were partially negated by selective removal of pathogenic soluble tau aggregates from brain. We found that similar to trans-neuronal transmission of pathogenic forms of tau, soluble tau aggregates are internalized by brain microvascular endothelial cells in a heparin-sensitive manner and induce microtubule destabilization, block endothelial nitric oxide synthase (eNOS) activation, and potently induce endothelial cell senescence that was recapitulated in vivo in microvasculature of P301S(PS19) mice. Our studies suggest that soluble pathogenic tau aggregates mediate AD-like brain microvascular deficits in a mouse model of tauopathy, which may arise from endothelial cell senescence and eNOS dysfunction triggered by internalization of soluble tau aggregates.

 

Dr. Veronica Galvan named Director of Oklahoma Nathan Shock Center of Excellence

Dr. Galvan’s research interests are focused on studies of biological mechanisms that link aging to the pathogenesis of age-associated neurological disease, that she pioneered.  Her laboratory provided the first evidence for a role of ‘pillar’ molecular mediators of aging in the etiology of Alzheimer’s disease and related dementias. The goal of her research group is to define molecular processes that underlie age-associated neurological disease and identify translational interventions that promote nervous system healthspan and improve quality of life.  Dr. Galvan has been actively involved in the leadership of center and program grants including but not limited to Nathan Shock Center programs. She has contributed more than 80 publications, some cited over 1000 times, has been recognized by prestigious awards, and is a Fellow of the American Aging Association. Dr. Galvan served as President of the American Aging Association and currently serves as Editor-in-Chief of Geroscience, the Journal of the American Aging Association.  In addition to directing the Oklahoma Nathan Shock Center on Aging Dr. Galvan serves as Co-Director of the Oklahoma Center for Geroscience and Healthy Brain Aging and Co-Director of the Geroscience Center of Biomedical Research Excellence at OUHSC.  She is also a Research Career Scientist at the US Department of Veterans Affairs Oklahoma City VA Medical Center.

Dr. Galvan pioneered the studies of biological mechanisms that link aging to the pathogenesis of age-associated neurological disease.  Her laboratory provided the first evidence for a role of ‘pillar’ molecular mediators of aging in the etiology of Alzheimer’s disease and related dementias. The goal of her research group is to define molecular processes that underlie age-associated neurological disease and identify translational interventions that promote nervous system healthspan and improve quality of life.  Dr. Galvan has been actively involved in the leadership of center and program grants including but not limited to Nathan Shock Center programs. She has contributed more than 80 publications, some cited over 1000 times, has been recognized by prestigious awards, and is a Fellow of the American Aging Association. Dr. Galvan served as President of the American Aging Association and currently serves as Editor-in-Chief of Geroscience, the Journal of the American Aging Association.  In addition to directing the Oklahoma Nathan Shock Center on Aging Dr. Galvan serves as Co-Director of the Oklahoma Center for Geroscience and Healthy Brain Aging and Co-Director of the Geroscience Center of Biomedical Research Excellence at OUHSC.  She is also a Research Career Scientist at the US Department of Veterans Affairs Oklahoma City VA Medical Center.