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A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid.
Sweeney, Melanie D; Sagare, Abhay P; Pachicano, Maricarmen; Harrington, Michael G; Joe, Elizabeth; Chui, Helena C; Schneider, Lon S; Montagne, Axel; Ringman, John M; Fagan, Anne M; Morris, John C; Pa, Judy; Nation, Daniel A; Toga, Arthur W; Zlokovic, Berislav V.
Afiliação
  • Sweeney MD; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Sagare AP; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Pachicano M; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Harrington MG; Huntington Medical Research Institutes, Pasadena, California, USA.
  • Joe E; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Chui HC; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Schneider LS; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Montagne A; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Ringman JM; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Fagan AM; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Morris JC; Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, California, USA.
  • Pa J; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Nation DA; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Toga AW; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Zlokovic BV; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Alzheimers Dement ; 16(6): 821-830, 2020 06.
Article em En | MEDLINE | ID: mdl-32301266
ABSTRACT

INTRODUCTION:

Blood-brain barrier (BBB) breakdown and loss of brain capillary pericytes contributes to cognitive impairment. Pericytes express platelet-derived growth factor receptor-ß (PDGFRß) that regulates brain angiogenesis and blood vessel stability. Elevated soluble PDGFRß (sPDGFRß) 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 sPDGFRß immunoassay that was used to measure sPDGFRß in human CSF from 147 individuals.

RESULTS:

We developed standard operating procedures for a highly sensitive and reproducible sPDGFRß immunoassay with a dynamic range from 100 to 26,000 pg/mL, and confirmed elevated CSF sPDGFRß 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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Pericitos / Receptor beta de Fator de Crescimento Derivado de Plaquetas / Disfunção Cognitiva Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Pericitos / Receptor beta de Fator de Crescimento Derivado de Plaquetas / Disfunção Cognitiva Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article