Supplement: Neurovascular Astrocyte Dysfunction in VCID

Grants and Contracts Details


Down syndrome (DS) individuals develop Alzheimer’s disease (AD) neuropathology by 40 years of age, with clinical dementia typically observed at ages over 50 years. At the University of Kentucky, we have been following DS individuals over the age of 25 for eight years. These individuals undergo cognitive testing and MRI imaging, as well as giving blood samples for fluid biomarker studies. Novel findings already published from the longitudinal study include early white matter disruptions, unique neuroinflammatory responses, and altered brain metabolism. Recent findings from the study highlight early cerebrovascular changes in the DS brain. As a result of these recent, exciting findings, we propose to explore neurovascular astrocyte changes in the DS brain, and explore some recently identified, novel fluid biomarkers that we find associate significantly with small vessel ischemic disease and vascular cognitive impairment. These data will further add to the parent RO1 grant. Our overarching hypothesis is that DS brains show neurovascular astrocyte degeneration early in the disease process and this is accompanied by changes in endothelial and microglial cell activation. To test our hypotheses, we propose two specific aims for this supplement: Specific Aim 1: Test the hypothesis that neurovascular astrocyte degeneration is present early in the DS brain and is associated with cerebrovascular pathology. Specific Aim 2: Test the hypothesis that endothelial activation and a neuroinflammatory response accompanies cerebrovascular pathologies in a longitudinally followed DS cohort.
Effective start/end date8/1/175/31/20


  • National Institute of Neurological Disorders & Stroke


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