{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T16:46:40Z","timestamp":1770482800368,"version":"3.49.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2011,1,31]],"date-time":"2011-01-31T00:00:00Z","timestamp":1296432000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0015809","type":"journal-article","created":{"date-parts":[[2011,1,31]],"date-time":"2011-01-31T16:54:20Z","timestamp":1296492860000},"page":"e15809","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":56,"title":["Increased Prothrombin, Apolipoprotein A-IV, and Haptoglobin in the Cerebrospinal Fluid of Patients with Huntington's Disease"],"prefix":"10.1371","volume":"6","author":[{"given":"Yen-Chu","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yih-Ru","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu-Yun","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Chun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen-Yung","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiung-Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2011,1,31]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.","volume":"72","author":"ME MacDonald","year":"1993","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.","volume":"277","author":"M DiFiglia","year":"1997","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nature06022","article-title":"Global changes to the ubiquitin system in Huntington's disease.","volume":"448","author":"EJ Bennett","year":"2007","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/brain\/awm312","article-title":"Chromosomal profiles of gene expression in Huntington's disease.","volume":"131","author":"AN Anderson","year":"2008","journal-title":"Brain"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"7899","DOI":"10.1523\/JNEUROSCI.1396-07.2007","article-title":"Dopaminergic signaling and striatal neurodegeneration in Huntington's disease.","volume":"27","author":"TS Tang","year":"2007","journal-title":"J Neurosci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1093\/brain\/awl027","article-title":"Huntington disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles.","volume":"129","author":"BR Underwood","year":"2006","journal-title":"Brain"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1212\/01.WNL.0000031791.10922.CF","article-title":"Weight loss in early stage of Huntington's disease.","volume":"59","author":"L Djouss\u00e9","year":"2002","journal-title":"Neurology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbrc.2007.05.093","article-title":"Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington's disease patients.","volume":"359","author":"CM Chen","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/mds.20373","article-title":"Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease.","volume":"20","author":"C Saft","year":"2005","journal-title":"Mov Disord"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/WCO.0b013e328304b692","article-title":"Pathophysiology of Huntington's disease: from huntingtin functions to potential treatments.","volume":"21","author":"E Roze","year":"2008","journal-title":"Curr Opin Neurol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/hmg\/ddl467","article-title":"Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space.","volume":"16","author":"AN Strehlow","year":"2007","journal-title":"Hum Mol Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1074\/mcp.M800231-MCP200","article-title":"Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease.","volume":"8","author":"Q Fang","year":"2009","journal-title":"Mol Cell Proteomics"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1046\/j.1471-4159.2001.00673.x","article-title":"N(epsilon)-(gamma-L-glutamyl)-L-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease.","volume":"79","author":"TM Jeitner","year":"2001","journal-title":"J Neurochem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1471-4159.2008.05350.x","article-title":"Increased levels of gamma-glutamylamines in Huntington disease CSF.","volume":"106","author":"TM Jeitner","year":"2008","journal-title":"J Neurochem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0197-4580(01)00224-X","article-title":"N(epsilon)(gamma-glutamyl)lysine in cerebrospinal fluid marks Alzheimer type and vascular dementia.","volume":"22","author":"Z Nemes","year":"2001","journal-title":"Neurobiol Aging"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/ddr.10098","article-title":"Transglutaminase-mediated crosslinking of neural proteins in Alzheimer's disease and other primary dementias.","volume":"56","author":"M S\u00e1rv\u00e1ri","year":"2002","journal-title":"Drug Develop Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1212\/WNL.52.5.1104","article-title":"Cerebrospinal fluid F2-isoprostanes are elevated in Huntington's disease.","volume":"52","author":"TJ Montine","year":"1999","journal-title":"Neurology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1002\/mds.21447","article-title":"Cocaine- and amphetamine-regulated transcript is increased in Huntington disease.","volume":"22","author":"M Bj\u00f6rkqvist","year":"2007","journal-title":"Mov Disord"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.parkreldis.2008.05.012","article-title":"Levels of the light subunit of neurofilament triplet protein in cerebrospinal fluid in Huntington's disease.","volume":"15","author":"R Constantinescu","year":"2009","journal-title":"Parkinsonism Relat Disord"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1084\/jem.20080178","article-title":"A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.","volume":"205","author":"M Bj\u00f6rkqvist","year":"2008","journal-title":"J Exp Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1021\/pr0700753","article-title":"Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates.","volume":"6","author":"A Dalrymple","year":"2007","journal-title":"J Proteome Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/mds.870110204","article-title":"Unified Huntington's Disease Rating Scale: reliability and consistency.","volume":"11","year":"1996","journal-title":"Mov Disord"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/oxfordjournals.jbchem.a124565","article-title":"Blood coagulation factor Xa interacts with a linear sequence of the kringle 2 domain of prothrombin.","volume":"116","author":"H Taneda","year":"1994","journal-title":"J Biochem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1055\/s-0037-1615780","article-title":"Biochemistry and physiology of blood coagulation.","volume":"82","author":"KG Mann","year":"1999","journal-title":"Thromb Haemost"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1160\/TH08-03-0131","article-title":"Prothrombin\/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: localization, expression and participation in neurodegenerative diseases.","volume":"100","author":"E Sokolova","year":"2008","journal-title":"Thromb Haemost"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/01.jnen.0000196133.74087.cb","article-title":"Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain.","volume":"65","author":"T Arai","year":"2006","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.brainresrev.2007.08.002","article-title":"Protease-activated receptors in the brain: receptor expression, activation, and functions in neurodegeneration and neuroprotection.","volume":"56","author":"W Luo","year":"2007","journal-title":"Brain Res Rev"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1046\/j.0022-3042.2001.00745.x","article-title":"Participation of protease-activated receptor-1 in thrombin-induced microglial activation.","volume":"80","author":"Z Suo","year":"2002","journal-title":"J Neurochem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"C1351","DOI":"10.1152\/ajpcell.00001.2002","article-title":"Thrombin (PAR-1)-induced proliferation in astrocytes via MAPK involves multiple signaling pathways.","volume":"283","author":"H Wang","year":"2002","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jneuroim.2009.07.005","article-title":"Prothrombin kringle-2-induced oxidative stress contributes to the death of cortical neurons in vivo and in vitro: role of microglial NADPH oxidase.","volume":"214","author":"SY Won","year":"2009","journal-title":"J Neuroimmunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"5877","DOI":"10.1523\/JNEUROSCI.23-13-05877.2003","article-title":"Thrombin-induced microglial activation produces degeneration of nigral dopaminergic neurons in vivo.","volume":"23","author":"SH Choi","year":"2003","journal-title":"J Neurosci"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1111\/j.1471-4159.2005.03503.x","article-title":"Inhibition of thrombin-induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo.","volume":"95","author":"SH Choi","year":"2005","journal-title":"J Neurochem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0969-9961(03)00085-8","article-title":"Thrombin induces nigral dopaminergic neurodegeneration in vivo by altering expression of death-related proteins.","volume":"14","author":"SH Choi","year":"2003","journal-title":"Neurobiol Dis"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s12035-009-8097-5","article-title":"Targeting Glial Cells to Elucidate the Pathogenesis of Huntington's Disease.","volume":"14","author":"HY Hsiao","year":"2010","journal-title":"Mol Neurobiol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.physbeh.2008.05.022","article-title":"Characterization of apolipoprotein A-IV in brain areas involved in energy homeostasis.","volume":"95","author":"L Shen","year":"2008","journal-title":"Physiol Behav"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1210\/en.2006-1596","article-title":"Hypothalamic apolipoprotein A-IV is regulated by leptin.","volume":"148","author":"L Shen","year":"2007","journal-title":"Endocrinology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev.nutr.21.1.231","article-title":"The role of apolipoprotein A-IV in the regulation of food intake.","volume":"21","author":"P Tso","year":"2001","journal-title":"Annu Rev Nutr"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1172\/JCI116395","article-title":"Suppression of food intake by apolipoprotein A-IV is mediated through the central nervous system in rats.","volume":"91","author":"K Fujimoto","year":"1993","journal-title":"J Clin Invest"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1751-553X.2007.00898.x","article-title":"Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases.","volume":"29","author":"K Carter","year":"2007","journal-title":"Int J Lab Hematol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"15819","DOI":"10.1523\/JNEUROSCI.3776-09.2009","article-title":"Neuroprotective role of haptoglobin after intracerebral hemorrhage.","volume":"29","author":"X Zhao","year":"2009","journal-title":"J Neurosci"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1097\/01.wcb.0000037989.07114.d1","article-title":"Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats.","volume":"22","author":"MY Lee","year":"2002","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1089\/0897715041526212","article-title":"Proteome study of human cerebrospinal fluid following traumatic brain injury indicates fibrin(ogen) degradation products as trauma-associated markers.","volume":"21","author":"A Conti","year":"2004","journal-title":"J Neurotraum"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/prca.200600949","article-title":"Elevated haptoglobin level of cerebrospinal fluid in Guillain-Barre Syndrome revealed by proteomics analysis.","volume":"1","author":"KH Chang","year":"2007","journal-title":"Proteomics - Clin Appl"},{"key":"ref44","first-page":"225","article-title":"Abnormal penetration of haptoglobin through the blood-brain-barrier (BBB) into the cerebro-spinal fluid (CSF) in Alzheimer's disease patients.","volume":"91","author":"L Pantoni","year":"1995","journal-title":"Acta Neurol Scand"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s00701-006-0787-4","article-title":"Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics.","volume":"148","author":"X Li","year":"2006","journal-title":"Acta Neurochir (Wien)"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1007\/s11033-009-9574-7","article-title":"Proteome analysis of haptoglobin in cerebrospinal fluid of neuromyelitis optica.","volume":"37","author":"S Bai","year":"2010","journal-title":"Mol Biol Rep"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/elps.200405866","article-title":"An investigation into the human serum \u201cinteractome\u201d.","volume":"25","author":"M Zhou","year":"2004","journal-title":"Electrophoresis"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0015809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,8]],"date-time":"2019-06-08T03:11:34Z","timestamp":1559963494000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0015809"}},"subtitle":[],"editor":[{"given":"Mark","family":"Smith","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2011,1,31]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2011,1,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0015809","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,31]]}}}