Development of a novel, sensitive translational immunoassay to detect plasma glial fibrillary acidic protein (GFAP) after murine traumatic brain injury
department or school: Applied Science, Faculty of
department or school: Medicine, Faculty of
department or school: Other UBC
department or school: Biomedical Engineering, School of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
identifier citation: Alzheimer's Research & Therapy. 2021 Mar 07;13(1):58
contributor: Djavad Mowafaghian Centre for Brain Health
contributor: International Collaboration on Repair Discoveries
rights copyright: The Author(s)
creator: Button, Emily B.
creator: Cheng, Wai H.
creator: Barron, Carlos
creator: Cheung, Honor
creator: Bashir, Asma
creator: Cooper, Jennifer
creator: Gill, Jasmine
creator: Stukas, Sophie
creator: Baron, David C.
creator: Robert, Jerome
creator: Rowe, Elyn M.
creator: Cripton, Peter Alec, 1965-
creator: Wellington, Cheryl L.
issued: 2021-03-10T18:08:25Z
issued: 2021-03-07
description: Background: Glial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for several neurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. In humans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computed tomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAP in preclinical models are not yet available. Methods: We developed and validated a novel sensitive GFAP immunoassay assay for mouse plasma on the Meso Scale Discovery immunoassay platform and validated assay performance for robustness, precision, limits of quantification, dilutional linearity, parallelism, recovery, stability, selectivity, and pre-analytical factors. To provide proof-of-concept data for this assay as a translational research tool for TBI and Alzheimer’s disease (AD), plasma GFAP was measured in mice exposed to TBI using the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model and in APP/PS1 mice with normal or reduced levels of plasma high-density lipoprotein (HDL). Results: We performed a partial validation of our novel assay and found its performance by the parameters studied was similar to assays used to quantify human GFAP in clinical neurotrauma blood specimens and to assays used to measure murine GFAP in tissues. Specifically, we demonstrated an intra-assay CV of 5.0%, an inter-assay CV of 7.2%, a lower limit of detection (LLOD) of 9.0 pg/mL, a lower limit of quantification (LLOQ) of 24.8 pg/mL, an upper limit of quantification (ULOQ) of at least 16,533.9 pg/mL, dilution linearity of calibrators from 20 to 200,000 pg/mL with 90–123% recovery, dilution linearity of plasma specimens up to 32-fold with 96–112% recovery, spike recovery of 67–100%, and excellent analyte stability in specimens exposed to up to 7 freeze-thaw cycles, 168 h at 4 °C, 24 h at room temperature (RT), or 30 days at − 20 °…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/77499
note: RESEARCH Open AccessDevelopment of a novel, sensitivetranslational immunoassay to detectplasma glial fibrillary acidic protein (GFAP)after murine traumatic brain injuryEmily B. Button1,2, Wai Hang Cheng1,2, Carlos Barron1,2, Honor Cheung1,2, Asma Bashir1,2, Jennifer Cooper1,2,Jasmine Gill1,2, Sophie Stukas1,2, David C. Baron1,2, Jerome Robert1,2, Elyn M. Rowe1,2, Peter A. Cripton3,4 andCheryl L. Wellington1,2,3,4*AbstractBackground: Glial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for severalneurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. Inhumans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computedtomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAPin preclinical models are not yet available.Methods: We developed and validated a novel sensitive GFAP immunoassay assay for mouse plasma on the MesoScale Discovery immunoassay platform and validated assay performance for robustness, precision, limits ofquantification, dilutional linearity, parallelism, recovery, stability, selectivity, and pre-analytical factors. To provideproof-of-concept data for this assay as a translational research tool for TBI and Alzheimer’s disease (AD), plasmaGFAP was measured in mice exposed to TBI using the Closed Head Impact Model of Engineered RotationalAcceleration (CHIMERA) model and in APP/PS1 mice with normal or reduced levels of plasma high-densitylipoprotein (HDL).Results: We performed a partial validation of our novel assay and found its performance by the parameters studiedwas similar to assays used to quantify human GFAP in clinical neurotrauma blood specimens and to assays used tomeasure murine GFAP in tissues. Specifically, we demonstrated an intra-assay CV of 5.0%, an inter-assay CV of 7.2%,a lower limit of detection (LLOD) of 9.0 pg/mL, a lower limit of quantification (LLOQ) of 24.8 …
has type: Article
is shown at: 10.14288/1.0396093
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: BioMed Central
publisher DOI: 10.1186/s13195-021-00793-9
rights: Attribution 4.0 International (CC BY 4.0)
rights URI: http://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
subject: GFAP
subject: Plasma biomarker
subject: TBI
subject: CHIMERA
subject: Immunoassay
type: Text
identifier URI: http://hdl.handle.net/2429/77499