Cerebrospinal Fluid Biomarkers for Huntington's Disease

Journal of Huntington's Disease

Volumn 5, Issue 1, 2016, Pages 1-13

  Byrne, Lauren M ^a   Wild, Edward J ^a  

^a NATIONAL HOSPITAL FOR NEUROLOGY AND NEUROSURGERY   (United Kingdom)

Author keywords

biomarkers; cerebrospinal fluid; clinical trial; disease progression; Huntington's disease; neurodegenerative disease

Indexed keywords

4 AMINOBUTYRIC ACID; 5 HYDROXYINDOLEACETIC ACID; BIOLOGICAL MARKER; CORTICOTROPIN RELEASING FACTOR; HAPTOGLOBIN; HOMOVANILLIC ACID; HUNTINGTIN; INTERLEUKIN 6; INTERLEUKIN 8; KYNURENINE; NEUROTRANSMITTER; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE; PROTHROMBIN; QUINOLINIC ACID; TRYPTOPHAN;

ARTICLE; CEREBROSPINAL FLUID; DISEASE COURSE; ENZYME ACTIVITY; HUMAN; HUNTINGTON CHOREA; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; PROTEOMICS; ANIMAL; DISEASE MODEL; HUNTINGTON DISEASE; MEDICAL RESEARCH; MOUSE; PATHOPHYSIOLOGY;

ANIMALS; BIOMARKERS; BIOMEDICAL RESEARCH; DISEASE MODELS, ANIMAL; HUMANS; HUNTINGTON DISEASE; MICE;

EID: 84991384032     PISSN: 18796397     EISSN: 18796400     Source Type: Journal    
DOI: 10.3233/JHD-160196     Document Type: Article

References (85)

1. Wild EJ, Tabrizi SJ. Targets for future clinical trials in Huntington's disease: What's in the pipeline? Mov Disord. 2014;29:1434-45.
2. The Huntington's Disease Collaborative Research Group.A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993;72:971-83.
3. Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, et al. Huntington disease: Natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014;10:204-16.
4. Gallagher J. Landmark Huntington's trial starts-BBC News. BBC News Website 2015. http://www.bbc.co.uk/news/health-34552041 (accessed March 1, 2016).
5. Huntington Study Group. Unified Huntington's disease rating scale: Reliability and consistency. Mov Disord. 1996;11(2):136-42.
6. Scahill RI, Wild EJ, Tabrizi SJ. Biomarkers for Huntington's disease: An update. Expert Opin Med Diagn. 2012;6: 371-5.
7. Andreasson U, Perret-Liaudet A, van Waalwijk van Doorn LJC, Blennow K, Chiasserini D, Engelborghs S, et al. A Practical Guide to Immunoassay Method Validation. Front Neurol. 2015;6:179.
8. EMA. Guideline on bioanalytical method validation. EMEA, Comm Med Prod Hum Use. 2012;44:1-23.
9. Tabrizi SJ, Reilmann R, Roos RAC, Durr A, Leavitt B, Owen G, et al. Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACKHD study: Analysis of 24-month observational data. Lancet Neurol. 2012;11:42-53.
10. Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: Analysis of 36-month observational data. Lancet Neurol. 2013;12:637-49.
11. ClinicalTrials.gov. A Clinical Study in Subjects With Huntington's Disease to Assess the Efficacy and Safety of Three Oral Doses of Laquinimod. ClinicalTrials. gov, https://clinicaltrials.gov/ct2/show/NCT02215616 (accessed March 1, 2016).
12. ClinicalTrials.gov. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS-HTTRx in Patients With Early Manifest Huntington's Disease. ClinicalTrials. gov, https://clinicaltrials.gov/ct2/show/NCT02519036 (accessed March 1, 2016).
13. ClinicalTrials.gov. Randomized, Placebo Controlled Study Of The Efficacy And Safety Of PF-02545920 In Subjects With Huntington's Disease. ClinicalTrials. gov. https://clinicaltrials.gov/ct2/show/NCT02197130 (accessed March 1, 2016).
14. Wild EJ, Tabrizi SJ. Biomarkers for Huntington's disease. Expert Opin Med Diagn. 2008;2:47-62.
15. Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J Exp Med. 2008;205:1869-77.
16. Mochel F, Charles P, Seguin F, Barritault J, Coussieu C, Perin L, et al. Early energy deficit in Huntington disease: Identification of a plasma biomarker traceable during disease progression. PLoS One. 2007;2:e647.
17. Ciammola A, Sassone J, Cannella M, Calza S, Poletti B, Frati L, et al. Lowbrain-derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients. Am J Med Genet Part B Neuropsychiatr Genet. 2007;144:574-7.
18. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi JI, et al. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost. 2002;87:728-34.
19. Weiss A, Träger U, Wild EJ, Grueninger S, Farmer R, Landles C, et al. Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression. J Clin Invest. 2012;122:3731-6.
20. Reiber H. Proteins in cerebrospinal fluid and blood: Barriers, CSF flow rate and source-related dynamics. Restor Neurol Neurosci. 2003;21:79-96.
21. Rosén C, Zetterberg H. Cerebrospinal fluid biomarkers for pathological processes in Alzheimer's disease. Curr Opin Psychiatry. 2013;26:276-82.
22. Hall S, Surova Y, Öhrfelt A, Zetterberg H, Lindqvist D, Hansson O. CSF biomarkers and clinical progression of Parkinson disease. Neurology. 2015;84:57-63.
23. Peskind ER, Riekse R, Quinn JF, Kaye J, Clark CM, Farlow MR, et al. Safety and acceptability of the research lumbar puncture. Alzheimer Dis Assoc Disord. 2005;19:220-5.
24. Enna SJ, Wood JH, Snyder SH. γ-Aminobutyric acid (GABA) in human cerebrospinal fluid: Radioreceptor assay. J Neurochem. 1977;28:1121-4.
25. Enna SJ, Stern LZ,Wastek GJ,Yamamura HI. Cerebrospinal fluid gamma-aminobutyric acid variations in neurological disorders. Arch Neurol. 1977;34:683-5.
26. Manyam NVB, Hare TA, Katz L, Glaeser BS. Huntington's disease: Cerebrospinal fluid GABA levels in at-risk individuals. Arch Neurol. 1978;35:728.
27. Böhlen P, Tell G, Schechter PJ, Koch-Weser J, Agid Y, Coquillat G, et al. Cerebrospinal fluid homocarnosine in Huntington's disease. Life Sci. 1980;26:1009-12.
28. Bonnet AM, Tell G, Schechter PJ, Grove J, Saint-Hilaire MH, De Smet Y, et al. Cerebrospinal fluid GABA and homocarnosine concentrations in patients with Friedreich's ataxia, Parkinson's disease, and Huntington's chorea. Mov Disord. 1987;2:117-23.
29. Manyam NVB, Hare TA, Katz L. Effect of isoniazid on cerebrospinal fluid and plasma GABA levels in Huntington's disease. Life Sci. 1980;26:1303-8.
30. Tell G, Böhlen P, Schechter PJ, Koch-Weser J, Agid Y, Bonnet AM, et al. Treatment of Huntington disease with gamma-acetylenic GABA, an irreversible inhibitor of GABA-transaminase: Increased CSF GABA and homocarnosine without clinical amelioration. Neurology. 1981;31:207-11.
31. Manyam BV, Ferraro TN, Hare TA. Isoniazid-induced alteration of CSF neurotransmitter amino acids in Huntington's disease. Brain Res. 1987;408:125-30.
32. Manyam BV, Katz L, Hare TA, Kaniefski K, Tremblay RD. Isoniazid-induced elevation of CSF GABA levels and effects on chorea in Huntington's disease. Ann Neurol. 1981;10:35-7.
33. Manyam BV, Giacobini E, Colliver JA. Cerebrospinal fluid acetylcholinesterase and choline measurements in Huntington's disease. J Neurol. 1990;237:281-4.
34. Oepen G, Cramer H, Bernasconi R, Martin P. Huntington's disease-imbalance of free amino acids in the cerebrospinal fluid of patients and offspring at-risk. Arch Psychiatr Nervenkr. 1982;231:131-40.
35. Klawans HL Jr. A pharmacologic analysis of Huntington's chorea. Eur Neurol. 1970;4:148-63.
36. Klawans HL Jr. Cerebrospinal fluid homovanillic acid in Huntington's chorea. J Neurol Sci. 1971;13:277-9.
37. Mattsson B, Persson S-å. Cerebrospinal homovanillic acid and 5-hydroxy-indoleacetic acid in huntington's chorea. Acta Psychiatr Scand. 1974;50:245-59.
38. Curzon G, Gumpert J, Sharpe D. Amine metabolites in the cerebrospinal fluid in Huntington's chorea. J Neurol Neurosurg Psychiatry. 1972;35:514-9.
39. Garrett MC, Soares-da-Silva P. Increased cerebrospinal fluid dopamine and 3,4-dihydroxyphenylacetic acid levels in Huntington's disease: Evidence for an overactive dopaminergic brain transmission. J Neurochem. 1992;58: 101-6.
40. García Ruiz PJ, Mena MA, Sanchez Bernardos V, Díaz NeiraW, Gimenez Roldan S, Benitez J, et al. Cerebrospinal fluid homovanillic acid is reduced in untreated Huntington's disease. Clin Neuropharmacol. 1995;18:58-63.
41. Cooper AJL, Jeitner TM, Gentile V, Blass JP. Cross linking of polyglutamine domains catalyzed by tissue transglutaminase is greatly favored with pathological-length repeats: Does transglutaminase activity play a role in (CAG)n/Qn-expansion diseases? Neurochem Int. 2002;40: 53-67.
42. Jeitner TM, Bogdanov MB, Matson WR, Daikhin Y, Yudkoff M, Folk JE, et al. Nϵ-(γ-l-Glutamyl)-l-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease. J Neurochem. 2001;79:1109-12.
43. Jeitner TM, Matson WR, Folk JE, Blass JP, Cooper AJL. Increased levels of gamma-glutamylamines in Huntington disease CSF. J Neurochem. 2008;106:37-44.
44. Raptor Pharmaceutical Corp. Raptor Plans to Advance RP103 in a Registration Study in Huntington's Disease Based on Favorable Treatment Effects at 36 Months in CYST-HD Trial 2015. http://ir.raptorpharma.com/releasedetail.cfm?ReleaseID=946463 (accessed March 15, 2016).
45. Vécsei L, Szalárdy L, Fülöp F, Toldi J. Kynurenines in the CNS: Recent advances and new questions. Nat Rev Drug Discov. 2013;12:64-82.
46. Sathyasaikumar KV, Stachowski EK, Amori L, Guidetti P, Muchowski PJ, Schwarcz R. Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington's disease. J Neurochem. 2010;113:1416-25.
47. Bohár Z, Toldi J, Fülöp F, Vécsei L. Changing the face of kynurenines and neurotoxicity: Therapeutic considerations. Int J Mol Sci. 2015;16:9772-93.
48. Schwarcz R, Tamminga CA, Kurlan R, Shoulson I. Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia. Ann Neurol. 1988;24:580-2.
49. Heyes MP, Swartz KJ, Markey SP, Beal MF. Regional brain and cerebrospinal fluid quinolinic acid concentrations in Huntington's disease. Neurosci Lett. 1991;122:265-9.
50. Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain. 1992;115:1249-73.
51. Beal MF, Matson WR, Swartz KJ, Gamache PH, Bird ED. Kynurenine pathway measurements in Huntington's disease striatum: Evidence for reduced formation of kynurenic acid. J Neurochem. 1990;55(4):1327-39.
52. Chen X, Guo C, Kong J. Oxidative stress in neurodegenerative diseases. Neural Regen Res. 2012;7:376-85.
53. Montine TJ, Beal MF, Robertson D, Cudkowicz ME, Biaggioni I, O'Donnell H, et al. Cerebrospinal fluid F2-isoprostanes are elevated in Huntington's disease. Neurology. 1999;52:1104.
54. Montine TJ, Markesbery WR, Morrow JD, Roberts LJ. Cerebrospinal fluid F2-isoprostane levels are increased in Alzheimer's disease. Ann Neurol. 1998;44:410-3.
55. Huntington Study Group TREND-HD Investigators. Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: The TREND-HD study. Arch Neurol. 2008;65:1582-9.
56. National Institute of Neurological Disorders and Stroke. Announcement of 2CARE Early Study Closure 2014. http://www.ninds.nih.gov/disorders/clinical trials/2CAREEarly-Study-Closure.htm (accessed March 10, 2016).
57. Dalrymple A,Wild EJ, Joubert R, SathasivamK, Björkqvist M, Petersén A, et al. Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates. J Proteome Res. 2007;6:2833-40.
58. Träger U, Andre R, Lahiri N, Magnusson-Lind A, Weiss A, Grueninger S, et al. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation. Brain. 2014;137:819-33.
59. Aronson NN, Blanchard CJ, Madura JD. Homology modeling of glycosyl hydrolase family 18 enzymes and proteins. J Chem Inf Comput Sci. 1997;37:999-1005.
60. Vinther-Jensen T, Budtz-Jørgensen E, Simonsen AH, Nielsen JE, Hjermind LE. YKL-40 in cerebrospinal fluid in Huntington's disease - a role in pathology or a nonspecific response to inflammation? Parkinsonism Relat Disord. 2014;20:1301-3.
61. Huang Y-C, Wu Y-R, Tseng M-Y, Chen Y-C, Hsieh S-Y, Chen C-M. Increased prothrombin, apolipoprotein A-IV, and haptoglobin in the cerebrospinal fluid of patients with Huntington's disease. PLoS One. 2011;6:e15809.
62. Pantoni L, Inzitari D. Abnormal penetration of haptoglobin through the blood-brain-barrier (BBB) into the cerebrospinal fluid (CSF) in Alzheimer's disease patients. Acta Neurol Scand. 1995;81:225.
63. Conti A, Sanchez-Ruiz Y, Bachi A, Beretta L, Grandi E, Beltramo M, et al. Proteome study of human cerebrospinal fluid following traumatic brain injury indicates fibrin(ogen) degradation products as trauma-associated markers. J Neurotrauma. 2004;21:854-63.
64. Peterseń Å. The role of hypothalamic and neuroendocrine changes in the pathogenesis of huntington's disease-Current understanding and implications for future treatments. Eur Neurol Rev. 2010;5:49-53.
65. Nemeroff CB, Widerlöv E, Bissette G, Walléus H, Karlsson I, Eklund K, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science. 1984;226:1342-4.
66. Post RM, Ballenger JC, Goodwin FK. Cerebrospinal Fluid Studies of Neurotransmitter Function in Manic and Depressive Illness. In: Wood JH, editor. Neurobiol. Cerebrospinal Fluid, New York: Springer US. 1980;685-717.
67. Kurlan R, Caine E, Rubin A, Nemeroff CB, Bissette G, Zaczek R, et al. Cerebrospinal fluid correlates of depression in Huntington's disease. Arch Neurol. 1988;45:881-3.
68. Popovic V, Svetel M, Djurovic M, Petrovic S, Doknic M, Pekic S, et al. Circulating and cerebrospinal fluid ghrelin and leptin: Potential role in altered body weight in Huntington's disease. Eur J Endocrinol. 2004;151:451-5.
69. Meier A, Mollenhauer B, Cohrs S, Rodenbeck A, JordanW, Meller J, et al. Normal hypocretin-1 (orexin-A) levels in the cerebrospinal fluid of patients with Huntington's disease. Brain Res. 2005;1063:201-3.
70. Björkqvist M, Peterseń Å, Carroll J, Nielsen J, Ecker D, Mulder H, et al. Cerebrospinal fluid levels of orexin-A are not a clinically useful biomarker for Huntington disease. Clin Genet. 2006;70:78-9.
71. Gaus SE, Lin L, Mignot E. CSF hypocretin levels are normal in Huntington's disease patients. Sleep. 2005;28:1607-8.
72. Björkqvist M, Leavitt BR, Nielsen JE, Landwehrmeyer B, Ecker D, Mulder H, et al. Cocaine-and amphetamineregulated transcript is increased in Huntington disease. Mov Disord. 2007;22:1952-4.
73. Gabery S, MurphyK, Schultz K, LoyCT, McCusker E, Kirik D, et al. Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses. Acta Neuropathol. 2010;120:777-88.
74. Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6:131-44.
75. Constantinescu R, Romer M, Oakes D, Rosengren L, Kieburtz K. Levels of the light subunit of neurofilament triplet protein in cerebrospinal fluid in Huntington's disease. Parkinsonism Relat Disord. 2009;15:245-8.
76. Constantinescu R, Romer M, Zetterberg H, Rosengren L, Kieburtz K. Increased levels of total tau protein in the cerebrospinal fluid in Huntington's disease. Parkinsonism Relat Disord. 2011;17:714-5.
77. Lewczuk P, Beck G, Esselmann H, Bruckmoser R, Zimmermann R, Fiszer M, et al. Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid β peptides. Clin Chem. 2005;52:331-2.
78. Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD, et al. Identification of an important potential confound in CSF AD studies: Aliquot volume. Clin Chem Lab Med. 2013;51:2311-7.
79. Ge X, Yamamoto S, Tsutsumi S, Midorikawa Y, Ihara S, Wang SM, et al. Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005;86:127-41.
80. Fang Q, Strand A, LawW, Faca VM, FitzgibbonMP, Hamel N, et al. Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease. Mol Cell Proteomics. 2009;8:451-66.
81. Vinther-Jensen T, Simonsen AH, Budtz-Jørgensen E, Hjermind LE, Nielsen JE. Ubiquitin: A potential cerebrospinal fluid progression marker in Huntington's disease. Eur J Neurol. 2015;22(10):1378-84.
82. Dantuma NP, Bott LC. The ubiquitin-proteasome system in neurodegenerative diseases: Precipitating factor, yet part of the solution. Front Mol Neurosci. 2014;7:70.
83. Wild EJ, Boggio R, Langbehn D, Robertson N, Haider S, Miller JRC, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients. J Clin Invest. 2015;125:1-8.
84. Southwell AL, Smith SEP, Davis TR, Caron NS, Villanueva EB, Xie Y, et al. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression. Sci Rep. 2015;5:12166.
85. Tan Z, Dai W, van Erp TGM, Overman J, Demuro A, Digman MA, et al. Huntington's disease cerebrospinal fluid seeds aggregation of mutant huntingtin. Mol Psychiatry. 2015:1-8.