Melanie D Sweeney1, Abhay P Sagare1, Maricarmen Pachicano1, Michael G Harrington2, Elizabeth Joe3,4, Helena C Chui3,4, Lon S Schneider3,4,5, Axel Montagne1, John M Ringman3,4, Anne M Fagan6,7,8, John C Morris6,8, Judy Pa3,9, Daniel A Nation1,3,10, Arthur W Toga3,9, Berislav V Zlokovic1,3. 1. Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 2. Huntington Medical Research Institutes, Pasadena, California, USA. 3. Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 4. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 5. Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, California, USA. 6. Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. 7. The Hope Center for Neurodegenerative Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. 8. The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA. 9. Laboratory of Neuro Imaging (LONI), USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 10. Department of Psychology, University of Southern California, Los Angeles, California, USA.
Abstract
INTRODUCTION: Blood-brain barrier (BBB) breakdown and loss of brain capillary pericytes contributes to cognitive impairment. Pericytes express platelet-derived growth factor receptor-β (PDGFRβ) that regulates brain angiogenesis and blood vessel stability. Elevated soluble PDGFRβ (sPDGFRβ) levels in cerebrospinal fluid (CSF) indicate pericyte injury and BBB breakdown, which is an early biomarker of human cognitive dysfunction. METHODS: A combination of reagents and conditions were tested, optimized, and validated on the Meso Scale Discovery electrochemiluminescence platform to develop a new sPDGFRβ immunoassay that was used to measure sPDGFRβ in human CSF from 147 individuals. RESULTS: We developed standard operating procedures for a highly sensitive and reproducible sPDGFRβ immunoassay with a dynamic range from 100 to 26,000 pg/mL, and confirmed elevated CSF sPDGFRβ levels in individuals with cognitive dysfunction. DISCUSSION: This assay could be applied at different laboratories to study brain pericytes and microvascular damage in relation to cognition in disorders associated with neurovascular and cognitive dysfunction.
INTRODUCTION: Blood-brain barrier (BBB) breakdown and loss of brain capillary pericytes contributes to cognitive impairment. Pericytes express platelet-derived growth factor receptor-β (PDGFRβ) that regulates brain angiogenesis and blood vessel stability. Elevated soluble PDGFRβ (sPDGFRβ) levels in cerebrospinal fluid (CSF) indicate pericyte injury and BBB breakdown, which is an early biomarker of humancognitive dysfunction. METHODS: A combination of reagents and conditions were tested, optimized, and validated on the Meso Scale Discovery electrochemiluminescence platform to develop a new sPDGFRβ immunoassay that was used to measure sPDGFRβ in human CSF from 147 individuals. RESULTS: We developed standard operating procedures for a highly sensitive and reproducible sPDGFRβ immunoassay with a dynamic range from 100 to 26,000 pg/mL, and confirmed elevated CSF sPDGFRβ levels in individuals with cognitive dysfunction. DISCUSSION: This assay could be applied at different laboratories to study brain pericytes and microvascular damage in relation to cognition in disorders associated with neurovascular and cognitive dysfunction.
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