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A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid
Author(s) -
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.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12061
Subject(s) - cerebrospinal fluid , pericyte , biomarker , immunoassay , blood–brain barrier , medicine , concussion , angiogenesis , pathology , immunology , chemistry , in vitro , central nervous system , antibody , biochemistry , poison control , environmental health , injury prevention , endothelial stem cell
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.