A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid

Melanie D Sweeney; Abhay P Sagare; Maricarmen Pachicano; Michael G Harrington; Elizabeth Joe; Helena C Chui; Lon S Schneider; Axel Montagne; John M Ringman; Anne M Fagan; John C Morris; Judy Pa; Daniel A Nation; Arthur W Toga; Berislav V Zlokovic

doi:10.1002/alz.12061

A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid

Melanie D Sweeney, Abhay P Sagare, Maricarmen Pachicano, Michael G Harrington, Elizabeth Joe, Helena C Chui, Lon S Schneider, Axel Montagne, John M Ringman, Anne M Fagan, John C Morris, Judy Pa, Daniel A Nation, Arthur W Toga, Berislav V Zlokovic

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	821-830
Number of pages	10
Journal	Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume	16
Issue number	6
DOIs	https://doi.org/10.1002/alz.12061
Publication status	Published - Jun 2020

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10.1002/alz.12061

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Sweeney, M. D., Sagare, A. P., Pachicano, M., Harrington, M. G., Joe, E., Chui, H. C., Schneider, L. S., Montagne, A., Ringman, J. M., Fagan, A. M., Morris, J. C., Pa, J., Nation, D. A., Toga, A. W., & Zlokovic, B. V. (2020). A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 16(6), 821-830. https://doi.org/10.1002/alz.12061

@article{a1b2058cdd9e4a0cba0156e6946d58eb,

title = "A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid",

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.",

author = "Sweeney, {Melanie D} and Sagare, {Abhay P} and Maricarmen Pachicano and Harrington, {Michael G} and Elizabeth Joe and Chui, {Helena C} and Schneider, {Lon S} and Axel Montagne and Ringman, {John M} and Fagan, {Anne M} and Morris, {John C} and Judy Pa and Nation, {Daniel A} and Toga, {Arthur W} and Zlokovic, {Berislav V}",

note = "{\textcopyright} 2020 the Alzheimer's Association.",

year = "2020",

month = jun,

doi = "10.1002/alz.12061",

language = "English",

volume = "16",

pages = "821--830",

journal = "Alzheimer's & Dementia: The Journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "Wiley",

number = "6",

}

Sweeney, MD, Sagare, AP, Pachicano, M, Harrington, MG, Joe, E, Chui, HC, Schneider, LS, Montagne, A, Ringman, JM, Fagan, AM, Morris, JC, Pa, J, Nation, DA, Toga, AW & Zlokovic, BV 2020, 'A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid', Alzheimer's & Dementia: The Journal of the Alzheimer's Association, vol. 16, no. 6, pp. 821-830. https://doi.org/10.1002/alz.12061

TY - JOUR

T1 - A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid

AU - Sweeney, Melanie D

AU - Sagare, Abhay P

AU - Pachicano, Maricarmen

AU - Harrington, Michael G

AU - Joe, Elizabeth

AU - Chui, Helena C

AU - Schneider, Lon S

AU - Montagne, Axel

AU - Ringman, John M

AU - Fagan, Anne M

AU - Morris, John C

AU - Pa, Judy

AU - Nation, Daniel A

AU - Toga, Arthur W

AU - Zlokovic, Berislav V

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

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DO - 10.1002/alz.12061

M3 - Article

C2 - 32301266

SN - 1552-5260

VL - 16

SP - 821

EP - 830

JO - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

JF - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

IS - 6

ER -

A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid

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