TY - JOUR T1 - Cerebrospinal fluid and blood levels of GFAP in Alexander disease JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0080-15.2015 SP - ENEURO.0080-15.2015 AU - Paige L. Jany AU - Guillermo E. Agosta AU - William S. Benko AU - Jens C. Eickhoff AU - Stephanie R. Keller AU - Wolfgang Köehler AU - David Koeller AU - Soe Mar AU - Sakkubai Naidu AU - Jayne Marie Ness AU - Davide Pareyson AU - Deborah L. Renaud AU - Ettore Salsano AU - Raphael Schiffmann AU - Julie Simon AU - Adeline Vanderver AU - Florian Eichler AU - Marjo S. van der Knaap AU - Albee Messing Y1 - 2015/09/15 UR - http://www.eneuro.org/content/early/2015/09/15/ENEURO.0080-15.2015.abstract N2 - 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. ER -