RT Journal Article SR Electronic T1 Cerebrospinal fluid and blood levels of GFAP in Alexander disease JF eneuro JO eneuro FD Society for Neuroscience SP ENEURO.0080-15.2015 DO 10.1523/ENEURO.0080-15.2015 A1 Paige L. Jany A1 Guillermo E. Agosta A1 William S. Benko A1 Jens C. Eickhoff A1 Stephanie R. Keller A1 Wolfgang Köehler A1 David Koeller A1 Soe Mar A1 Sakkubai Naidu A1 Jayne Marie Ness A1 Davide Pareyson A1 Deborah L. Renaud A1 Ettore Salsano A1 Raphael Schiffmann A1 Julie Simon A1 Adeline Vanderver A1 Florian Eichler A1 Marjo S. van der Knaap A1 Albee Messing YR 2015 UL http://www.eneuro.org/content/early/2015/09/15/ENEURO.0080-15.2015.1.abstract AB 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 central nervous system. A key step in pathogenesis appears to be the accumulation of GFAP protein 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 – cerebrospinal fluid and blood. We find that GFAP levels are consistently elevated in the CSF of Alexander disease patients, but only occasionally and modestly in blood. These results provide the foundation for future studies that will explore whether GFAP levels can serve as a convenient means to monitor progression of disease and response to treatment.Significance Statement: GFAP is an intermediate filament protein that is predominantly expressed in astrocytes of the central nervous system. Although typically confined to the cytoplasm, GFAP is released at low levels into the extracellular space, and can appear at measurable levels in cerebrospinal fluid (CSF) and blood. Here we show that the fluid levels of GFAP increase markedly in Alexander disease, a genetic disorder that results from mutations in GFAP itself, particularly in the CSF. CSF analysis may therefore offer a relatively non-invasive means for indirectly monitoring the levels of GFAP in brain, and assessing the efficacy of future experimental treatments that are designed to reduce these levels.