Biomarkers of
Neuroinflammation
PROCEEDINGS OF A WORKSHOP
Lisa Bain, Noam I. Keren, and Sheena M. Posey Norris,
Rapporteurs
Forum on Neuroscience and
Nervous System Disorders
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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This activity was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; Brain Canada Foundation; Cohen Veterans Bioscience; the Department of Health and Human Services’ Food and Drug Administration (5R13FD005362-02) and National Institutes of Health (NIH) (HHSN26300089 [Under Master Base #DHHS-10002880]) through the National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH Blueprint for Neuroscience Research; Department of Veterans Affairs (VA240-14-C-0057); Eli Lilly and Company; Foundation for the National Institutes of Health; The Gatsby Charitable Foundation; George and Anne Ryan Institute for Neuroscience at The University of Rhode Island; Janssen Research & Development, LLC; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; National Multiple Sclerosis Society; National Science Foundation (BCS-1064270); One Mind; Pfizer Inc.; Pharmaceutical Product Development, LLC; Sanofi; Society for Neuroscience; and Takeda Development Center Americas, Inc. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for this project.
International Standard Book Number-13: 978-0-309-46365-2
International Standard Book Number-10: 0-309-46365-3
Digital Object Identifier: https://doi.org/10.17226/24854
Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2018 by the National Academy of Sciences. All rights reserved.
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Cover image courtesy of Dr. Gary Landreth, Case Western Reserve University, Cleveland, Ohio.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Biomarkers of neuroinflammation: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24854.
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PLANNING COMMITTEE ON BIOMARKERS OF NEUROINFLAMMATION1
RITA BALICE-GORDON (Co-Chair), Sanofi
LINDA BRADY (Co-Chair), National Institute of Mental Health
BRIAN CAMPBELL, MindImmune Therapeutics, Inc.
ROSA CANET-AVILES, Foundation for the National Institutes of Health
TIMOTHY COETZEE, National Multiple Sclerosis Society
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, Department of Veterans Affairs
ELIEZER MASLIAH, National Institute on Aging
PATRICIO O’DONNELL, Pfizer Inc. (until March 2017)
WILLIAM POTTER, National Institute of Mental Health
RICHARD RANSOHOFF, Biogen
BETH STEVENS, Harvard Medical School
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Division Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
NOAM I. KEREN, Associate Program Officer
DANIEL FLYNN, Senior Program Assistant
ANDREW M. POPE, Director, Board on Health Sciences Policy
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS1
STEVEN HYMAN (Chair), Broad Institute of Massachusetts Institute of Technology and Harvard University
STORY LANDIS (Vice Chair), Director Emeritus, National Institute of Neurological Disorders and Stroke
SUSAN AMARA, Society for Neuroscience
RITA BALICE-GORDON, Sanofi
KATJA BROSE, Chan Zuckerberg Initiative
EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology
DANIEL BURCH, Pharmaceutical Product Development, LLC
JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai
SARAH CADDICK, The Gatsby Charitable Foundation
ROSA CANET-AVILES, Foundation for the National Institutes of Health
MARIA CARRILLO, Alzheimer’s Association
E. ANTONIO CHIOCCA, Harvard Medical School
TIMOTHY COETZEE, National Multiple Sclerosis Society
JONATHAN COHEN, Princeton University
FAY LOMAX COOK, National Science Foundation
BILLY DUNN, Food and Drug Administration
JOSHUA GORDON, National Institute of Mental Health
HANK GREELY, Stanford University
RAQUEL GUR, University of Pennsylvania
MAGALI HAAS, Cohen Veterans Bioscience
RAMONA HICKS, One Mind
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, Department of Veterans Affairs
MICHAEL IRIZARRY, Eli Lilly and Company
INEZ JABALPURWALA, Brain Canada Foundation
FRANCES JENSEN, University of Pennsylvania
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
ALAN LESHNER, American Association for the Advancement of Science (Emeritus)
HUSSEINI MANJI, Janssen Research & Development, LLC
DAVID MICHELSON, Merck Research Laboratories
JAMES OLDS, National Science Foundation
ATUL PANDE, Tal Medical
STEVEN PAUL, Voyager Therapeutics, Inc.
RODERIC PETTIGREW, National Institute of Biomedical Imaging and Bioengineering
EMILIANGELO RATTI, Takeda Pharmaceuticals International
TAREK SAMAD, Pfizer Inc.
TODD SHERER, The Michael J. Fox Foundation for Parkinson’s Research
DAVID SHURTLEFF, National Center for Complementary and Integrative Health
PAUL SIEVING, National Eye Institute
NORA VOLKOW, National Institute on Drug Abuse
DOUG WILLIAMSON, Lundbeck
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Division Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
NOAM I. KEREN, Associate Program Officer
DANIEL FLYNN, Senior Program Assistant
JIM BANIHASHEMI, Financial Officer
HILARY BRAGG, Program Coordinator (until August 2017)
ANDREW M. POPE, Director, Board on Health Sciences Policy
Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
KATERNIA AKASSOGLOU, University of California, San Francisco
ELIEZER MASLIAH, National Institute on Aging
THOMAS MÖLLER, AbbVie Foundational Neuroscience Center
TAREK SAMAD, Pfizer R&D
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by JOSEPH T. COYLE, Harvard Medical School. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
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Contents
Organization of the Proceedings
2 Biomarkers of Neuroinflammation: Challenges and Potential Opportunities
Overview of Potential Opportunities
3 State of the Science of Neuroinflammation in Central Nervous System Disorders
Microglia and Neuroinflammation
Blood‒Brain Barrier Dysfunction
Fibrinogen and the Neurovascular Interface
4 Neuroinflammation in Disease
5 Neuroimaging Biomarkers: Current Initiatives and Opportunities