title: CSF and Blood Levels of GFAP in Alexander Disease
abstract: Alexander disease is a rare, progressive, and generally fatal neurological disorder that results from dominant mutations affecting the coding region of GFAP, the gene encoding glial fibrillary acidic protein, the major intermediate filament protein of astrocytes in the CNS. A key step in pathogenesis appears to be the accumulation of GFAP within astrocytes to excessive levels. Studies using mouse models indicate that the severity of the phenotype correlates with the level of expression, and suppression of GFAP expression and/or accumulation is one strategy that is being pursued as a potential treatment. With the goal of identifying biomarkers that indirectly reflect the levels of GFAP in brain parenchyma, we have assayed GFAP levels in two body fluids in humans that are readily accessible as biopsy sites: CSF and blood. We find that GFAP levels are consistently elevated in the CSF of patients with Alexander disease, but only occasionally and modestly elevated in blood. These results provide the foundation for future studies that will explore whether GFAP levels can serve as a convenient means to monitor the progression of disease and the response to treatment.
authors.affiliation: Waisman Center and Department of Comparative Biosciences, University of Wisconsin-Madison , Madison, Wisconsin 53705.
authors.forename: Paige L
authors.initials: PL
authors.lastname: Jany
authors.affiliation: Department of Child Neurology, Hospital Italiano School of Medicine , C1181ACH Buenos Aires, Argentina.
authors.forename: Guillermo E
authors.initials: GE
authors.lastname: Agosta
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20814.
authors.forename: William S
authors.initials: WS
authors.lastname: Benko
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison , Madison, Wisconsin 53792.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.affiliation: Division of Pediatric Neurology, Emory University , Atlanta, Georgia 30322.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Keller
authors.affiliation: Chefarzt der Klinik für Neurologie und neurologische Intensivmedizin , D-04799 Wermsdorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köehler
authors.affiliation: Department of Molecular & Medical Genetics, Oregon Health & Science University , Portland, Oregon 97239 ; Department of Pediatrics, Oregon Health & Science University , Portland, Oregon 97239.
authors.forename: David
authors.initials: D
authors.lastname: Koeller
authors.affiliation: Division of Pediatric Neurology, Washington University St. Louis , St. Louis, Missouri 63110.
authors.forename: Soe
authors.initials: S
authors.lastname: Mar
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21205.
authors.forename: Sakkubai
authors.initials: S
authors.lastname: Naidu
authors.affiliation: Division of Pediatric Neurology, University of Alabama-Birmingham , Birmingham, Alabama 35233.
authors.forename: Jayne
authors.initials: J
authors.lastname: Marie Ness
authors.affiliation: Department of Clinical Neurosciences, IRCCS Foundation, C. Besta Neurological Institute , 20133 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
authors.affiliation: Division of Child and Adolescent Neurology, Departments of Neurology and Pediatrics, Mayo Clinic , Rochester, Minnesota 55901.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Renaud
authors.affiliation: Department of Clinical Neurosciences, IRCCS Foundation, C. Besta Neurological Institute , 20133 Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Salsano
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20814.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Genomics Institute, Multi-Care Health System , Tacoma, Washington 98415.
authors.forename: Julie
authors.initials: J
authors.lastname: Simon
authors.affiliation: Children's Research Institute , Children's National Health System, Washington, DC 20010.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.affiliation: Massachusetts General Hospital , Boston, Massachusetts 02114.
authors.forename: Florian
authors.initials: F
authors.lastname: Eichler
authors.affiliation: Department of Child Neurology, Free University Medical Center , Amsterdam, 1007 MB, The Netherlands.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.affiliation: Waisman Center and Department of Comparative Biosciences, University of Wisconsin-Madison , Madison, Wisconsin 53705.
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
keywords: GFAP; astrocyte; biomarker