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Open Access 01-01-2012 | Movement Disorders - Review article

Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics

Authors: Manfred Gerlach, Walter Maetzler, Karl Broich, Harald Hampel, Lucas Rems, Torsten Reum, Peter Riederer, Albrecht Stöffler, Johannes Streffer, Daniela Berg

Published in: Journal of Neural Transmission | Issue 1/2012

Abstract

Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.

Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P (2001) Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology 56:730–736PubMed

Aarsland D, Andersen K, Larsen JP, Perry R, Wentzel-Larsen T, Lolk A, Kragh-Sorensen P (2004) The rate of cognitive decline in Parkinson disease. Arch Neurol 61:1906–1911PubMed

Abdi F, Quinn JF, Jankovic J, McIntosh M, Leverenz JB, Peskind E, Nixon R, Nutt J, Chung K, Zabetian C, Samii A, Lin M, Hattan S, Pan C, Wang Y, Jin J, Zhu D, Li GJ, Liu Y, Waichunas D, Montine TJ, Zhang J (2006) Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimers Dis 9:293–348PubMed

Adkin AL, Bloem BR, Allum JH (2005) Trunk sway measurements during stance and gait tasks in Parkinson’s disease. Gait Posture 22:240–249PubMed

Ahmed SS, Santosh W, Kumar S, Christlet HT (2009) Metabolic profiling of Parkinson’s disease: evidence of biomarker from gene expression analysis and rapid neural network detection. J Biomed Sci 16 (article no. 63) (doi:10.1186/1423-0127-16-63)

Alvarez-Erviti L, Rodriguez-Oroz MC, Cooper JM, Caballero C, Ferrer I, Obeso JA, Schapira AHV (2010) Chaperone-mediated autophagy markers in Parkinson disease brains. Arch Neurol 67:1464–1472PubMed

Athey RJ, Walker RW (2006) Demonstration of cognitive decline in Parkinson’s disease using the Cambridge Cognitive Assessment (Revised) (CAMCOG-R). Int J Geriatr Psychiatry 21:977–982PubMed

Beach TG, Sue LI, Walker DG, Lue LF, Connor DJ, Caviness JN, Sabbagh MN, Adler CH (2007) Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits. Acta Neuropathol 114:419–424PubMed

Benecke R, Strumper P, Weiss H (1993) Electron transfer complexes I and IV of platelets are abnormal in Parkinson’s disease but normal in Parkinson-plus syndromes. Brain 116:1451–1463PubMed

Berardelli A, Rothwell JC, Thompson PD, Hallett M (2001) Pathophysiology of bradykinesia in Parkinson’s disease. Brain 124:2131–2146PubMed

Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455PubMed

Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

Bloem BR, Roon KI, Delleman NJ, van Dijk JG, Roos RA (1997) Prolonged duration of standing up is an early dopa-sensitive abnormality in Parkinson’s disease. J Neurol Sci 146:41–44PubMed

Bogdanov M, Matson WR, Wang L, Matson T, Saunders-Pullman R, Bressman SS, Beal MF (2008) Metabolomic profiling to develop blood biomarkers for Parkinson’s disease. Brain 131:389–396PubMed

Braak H, Braak E, Yilmazer D, Schulz C, de Vos RAI, Jansen ENH (1995) Nigral and extranigral pathology in Parkinson’s disease. J Neural Transm (Suppl 46):15–31

Carpenter MG, Allum JH, Honegger F, Adkin AL, Bloem BR (2004) Postural abnormalities to multidirectional stance perturbations in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:1245–1254PubMed

Carpinella I, Crenna P, Calabrese E, Rabuffetti M, Mazzoleni P, Nemni R, Ferrarin M (2007) Locomotor function in the early stage of Parkinson’s disease. IEEE Trans Neural Syst Rehabil Eng 15:543–551PubMed

Chu YP, Dodiya H, Aebischer P, Olanow CW, Kordower JH (2009) Alterations in lysosomal and proteasomal markers in Parkinson’s disease: relationship to alpha-synuclein inclusions. Neurobiol Dis 35:385–398

Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM (1998) Folate, vitamin B-12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1149–1455

de Lau LM, Giesbergen PC, de Rijk MC, Hofman A, Koudstaal PJ, Breteler MM (2004) Incidence of parkinsonism and Parkinson disease in a general population: the Rotterdam Study. Neurology 63:1240–1244PubMed

De Nunzio AM, Nardone A, Schieppati M (2007) The control of equilibrium in Parkinson’s disease patients: delayed adaptation of balancing strategy to shifts in sensory set during a dynamic task. Brain Res Bulletin 74:258–270

Depboylu C, Schafer MKH, Arias-Carrion O, Oertel WH, Weihe E, Hoglinger GU (2011) Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease. J Neuropathol Exp Neurol 70:125–132PubMed

Diederich NJ, Raman R, Leurgans S, Goetz CG (2002) Progressive worsening of spatial and chromatic processing deficits in Parkinson disease. Arch Neurol 59:1249–1252PubMed

Dos Santos EF, Busanello EN, Miglioranza A, Zanatta A, Barchak AG, Vargas CR, Saute J, Rosa C, Carrion MJ, Camargo D, Dalbem A, da Costa JC, de Sousa Miguel SR, de Mello Rieder CR, Wajner M (2009) Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson’s disease. Metab Brain Dis 24:257–269PubMed

Double KL, Rowe DB, Carew-Jones FM, Hayes M, Chan DKY, Blackie J, Corbett A, Joffe R, Fung VS, Morris J, Riederer P, Gerlach M, Halliday GM (2009) Anti-melanin antibodies are increased in sera in Parkinson’s disease. Exp Neurol 217:297–301PubMed

Double KL, Reyes S, Werry EL, Halliday GM (2010) Selective cell death in neurodegeneration: why are some neurons spared in vulnerable regions? Prog Neurobiol 92:316–329PubMed

El-Agnaf OM, Salem SA, Paleologou KA, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D (2006) Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 20:419–425PubMed

Eller M, Williams DR (2009) Biological fluid biomarkers in neurodegenerative parkinsonism. Nat Rev Neurol 5:561–570PubMed

Elstner M, Morris CM, Heim K, Lichtner P, Bender A, Mehta D, Schulte C, Sharma M, Hudson G, Goldwurm S, Giovanetti A, Zeviani M, Burn DJ, McKeith IG, Perry RH, Jaros E, Kruger R, Wichmann HE, Schreiber S, Campbell H, Wilson JF, Wright AF, Dunlop M, Pistis G, Toniolo D, Chinnery PF, Gasser T, Klopstock T, Meitinger T, Prokisch H, Turnbull DM (2009) Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson’s disease gene. Ann Neurol 66:792–798PubMed

Fasano M, Alberio T, Lopiano L (2008) Peripheral biomarkers of Parkinson’s disease as early reporters of central neurodegeneration. Biomarkers Med 2:465–478

Forsaa EB, Larsen JP, Wentzel-Larsen T, Herlofson K, Alves G (2008) Predictors and course of health-related quality of life in Parkinson’s disease. Mov Disord 23:1420–1427PubMed

Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD, Rogers J, Siemers E, Trojanowski JQ (2003) Biological markers for therapeutic trials in Alzheimer’s disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer’s disease. Neurobiol Aging 24:521–536PubMed

Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344:710–719PubMed

Gasser T (2010) Identifying PD-causing genes and genetic susceptibility factors: current approaches and future prospects. Prog Brain Res 183:2–20

Gerlach M, Double K, Götz ME, Youdim MBH, Riederer P (2006) The role of iron in the pathogenesis of Parkinson’s disease. In: Sigel A, Sigel H, Sigel RKO (eds) Neurodegenerative diseases and metal ions. Metal ions in life sciences, vol 1. Wiley, Chichester, pp 125–149

Gerlach M, Hendrich A, Hueber R, Jost W, Winkler J, Woitalla D, Riederer P (2008) The early detection of Parkinson’s disease: unmet needs. Neurodegener Dis 5:137–139PubMed

Gjerstad MD, Wentzel-Larsen T, Aarsland D, Larsen JP (2007) Insomnia in Parkinson’s disease: frequency and progression over time. J Neurol Neurosurg Psychiatry 78:476–479PubMed

Godau J, Herfurth M, Kattner B, Gasser T, Berg D (2010) Increased serum insulin-like growth factor 1 in early idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 81:536–538PubMed

Goetz CG, Wuu J, Curgian LM, Leurgans S (2005) Hallucinations and sleep disorders in PD: six-year prospective longitudinal study. Neurology 64:81–86PubMed

Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Van Hilten JJ, LaPelle N (2007) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Mov Disord 22:41–47PubMed

Goldknopf IL, Sheta EA, Bryson J, Folsom B, Wilson C, Duty J, Yen AA, Appel SH (2006) Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson’s disease. Biochem Biophys Res Commun 342:1034–1039PubMed

Graham JM, Paley MN, Grunewald RA, Hoggard N, Griffiths PD (2000) Brain iron deposition in Parkinson’s disease imaged using the PRIME magnetic resonance sequence. Brain 123:2423–2431PubMed

Grunblatt E, Mandel S, Jacob-Hirsch J, Zeligson S, Amariglo N, Rechavi G, Li J, Ravid R, Roggendorf W, Riederer P, Youdim MB (2004) Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm 111:1543–1573PubMed

Grunblatt E, Zehetmayer S, Jacob CP, Muller T, Jost WH, Riederer P (2010) Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson’s disease. J Neural Transm 117:1387–1393PubMed

Haaxma CA, Bloem BR, Borm GF, Horstink MW (2008) Comparison of a timed motor test battery to the Unified Parkinson’s Disease Rating Scale-III in Parkinson’s disease. Mov Disord 23:1707–1717PubMed

Halperin I, Morelli M, Korczyn AD, Youdim MBH, Mandel SA (2009) Biomarkers for evaluation of clinical efficacy of multipotential neuroprotective drugs for Alzheimer’s and Parkinson’s diseases. Neurotherapeutics 6:128–140PubMed

Hampel H, Mitchell A, Blennow K, Frank RA, Brettschneider S, Weller L, Moller HJ (2004) Core biological marker candidates of Alzheimer’s disease—perspectives for diagnosis, prediction of outcome and reflection of biological activity. J Neural Transm 111:247–272PubMed

Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J, Herholz K, Bokde ALW, Jessen F, Hoessler YC, Sanhai WR, Zetterberg H, Woodcock J, Blennow K (2010) Biomarkers for Alzheimer’s disease: academic industry and regulatory perspectives. Nature Rev Drug Discov 9:560–574

Hassin-Baer S, Cohen O, Vakil E, Sela BA, Nitsan Z, Schwartz R, Chapman J, Tanne D (2006) Plasma homocysteine levels and Parkinson disease: disease progression, carotid intima-media thickness and neuropsychiatric complications. Clin Neuropharmacol 29:305–311PubMed

Hatano T, Kubo S, Sato S, Hattori N (2009) Pathogenesis of familial Parkinson’s disease: new insights based on monogenic forms of Parkinson’s disease. J Neurochem 111:1075–1193PubMed

Hausdorff JM (2008) The timed up and go test: more than meets the eye. Smolenice, Castle

Hilker R, Schweitzer K, Coburger S, Ghaemi M, Weisenbach S, Jacobs AH, Rudolf J, Herholz K, Heiss WD (2005) Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity. Arch Neurol 62:378–382PubMed

Hirotani M, Maita C, Niino M, Iguchi-Ariga AM, Hamada S, Ariga H, Sasaki H (2008) Correlation between DJ-1 levels in the cerebrospinal fluid and the progression of disabilities in multiple sclerosis patients. Mult Scler 14:1056–1060PubMed

Hirsch E, Graybiel A, Agid Y (1988) Melanized dopamine neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature 334:345–348PubMed

Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133:713–726PubMed

Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, Dhawan V, Eidelberg D (2007) Changes in network activity with the progression of Parkinson’s disease. Brain 130:1834–1846PubMed

Huxham F, Baker R, Morris ME, Iansek R (2008) Head and trunk rotation during walking turns in Parkinson’s disease. Mov Disord 23:1391–1397PubMed

Irizarry M, Gurol ME, Raju S, Diaz-Arrastia R, Locascio JJ, Tennis MRN, Hyman BT, Growdon JH, Greenberg SM, Bottiglieri T (2005) Association of homocysteine with plasma amyloid [beta] protein in aging and neurodegenerative disease. Neurology 65:1402–1408PubMed

Jellinger K (1991) Pathology of Parkinson’s disease. Changes other than the nigrostriatal pathway. Mol Chem Neuropathol 14:153–197PubMed

Johansen KK, Wang L, Aasly JP, White LR, Marson WR, Henchcliffe C, Beal MF, Bogdanov M (2009) Metabolomic profiling in LRRK2-related Parkinson’s disease. PLoS ONE 4:e7551PubMed

Kaddurah-Daouk R, Krishnan KR (2005) Metabolomics: a global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 34:173–186

Kahle PJ, Waak J, Gasser T (2009) DJ-1 and prevention of oxidative stress in Parkinson’s disease and other age-related disorders. Free Radic Biol Med 47:1354–1361PubMed

Kamanli A, Ardicoglu O, Ozgocmen S, Yoldas TK (2008) Bone mineral density in patients with Parkinson’s disease. Aging Clin Exp Res 20:277–279PubMed

Karlsen KH, Larsen JP, Tandberg E, Maeland JG (1999) Influence of clinical and demographic variables on quality of life in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 66:431–435PubMed

Katsarou Z, Bostantjopoulou S, Alevriadou A, Mentenopoulos G, Avraam X, Kiosseoglou G (1998) A longitudinal study of visuospatial discrimination in parkinsonian patients. Percept Mot Skills 86:171–180PubMed

Klein C, Schneider SA, Lang AE (2009) Hereditary parkinsonism: Parkinson’s disease look-alikes—an algorithm for clinicians to “Park” Genes and beyond. Mov Disord 24:2042–2058PubMed

Lang AE (2010) Clinical trials of disease-modifying therapies for neurodegenerative diseases: the challenges and the future. Nature Med 16:1223–1226PubMed

Liepelt I, Reimold M, Maetzler W, Godau J, Reischl G, Gaenslen A, Herbst H, Berg D (2009) Cortical hypometabolism assessed by a metabolic ratio in Parkinson’s disease primarily reflects cognitive deterioration-[18F]FDG-PET. Mov Disord 24:1504–1511PubMed

Linden D, Diehl RR, Berlit P (1997) Sympathetic cardiovascular dysfunction in long-standing idiopathic Parkinson’s disease. Clin Auton Res 7:311–314PubMed

Maetzler W, Berg D, Schalamberidze N, Melms A, Schott K, Mueller JC, Liaw L, Gasser T, Nitsch C (2007) Osteopontin is elevated in Parkinson’s disease and its absence leads to reduced neurodegeneration in the MPTP model. Neurobiol Dis 25:473–482PubMed

Maetzler W, Liepelt I, Berg D (2009a) Progression of Parkinson’s disease in the clinical phase: potential markers. Lancet Neurol 8:1158–1171PubMed

Maetzler W, Liepelt I, Reimold M, Reischl G, Solbach C, Becker C, Schulte C, Leyhe T, Keller S, Melms A, Gasser T, Berg D (2009b) Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics. Neurobiol Dis 34:107–112PubMed

Maetzler W, Schmid SP, Wurster I, Liepelt I, Gaenslen A, Gasser T, Berg D (2011) Reduced but not oxidized cerebrospinal fluid glutathione levels are lowered in Lewy body diseases. Mov Disord 26:176–181PubMed

Maita C, Tsuji S, Yabe I, Hamada S, Ogata A, Maita H, Iguchi-Ariga SMM, Sasaki H, Ariga H (2008) Secretion of DJ-1 into serum of patients with Parkinson’s disease. Neurosci Lett 431:86–89PubMed

Mamorita N, Iizuka T, Takeuchi A, Shirataka M, Ikeda N (2009) Development of a system for measurement and analysis of tremor using a three-axis accelerometer. Methods Inf Med 48:589–594PubMed

Mancini M, Zampieri C, Carlson-Kuhta P, Chiari L, Horak FB (2009) Anticipatory postural adjustments prior to step initiation are hypometric in untreated Parkinson’s disease: an accelerometer-based approach. Eur J Neurol 16:1028–1034PubMed

Marek K, Jennings D, Tamagnan G, Seibyl J (2008) Biomarkers for Parkinson’s disease: tools to assess Parkinson’s disease onset and progression. Ann Neurol (Suppl 64):S111–S121

Martins-de-Souza D (2010) Is the word “biomarker” being properly used by proteomics in neuroscience? Eur Arch Psychiatry Clin Neurosci 260:561–562PubMed

McCaddon A, Hudson B, Barber J, Lloyd A, Davies G, Regland B (2003) Alzheimer’s disease and total plasma aminothiols. Biol Psychiatry 53:254–260PubMed

Mesec A, Sega S, Trost M, Pogacnik T (1999) The deterioration of cardiovascular reflexes in Parkinson’s disease. Acta Neurol Scand 100:296–299PubMed

Michell AW, Lewis SJG, Foltynie T, Barker RA (2004) Biomarker and Parkinson’s disease. Brain 127:1693–1705PubMed

Milanov I (2002) Correlation between tremor parameters. Funct Neurol 17:19–23PubMed

Miller JW, Green R, Mungas DM, Reed BR, Jagust WJ (2002) Homocyteine, vitamin B-6, and vascular disease in AD patients. Neurology 58:1471–1475PubMed

Mollenhauer B, Trenkwalder C, von Ahsen N, Bibl M, Steinacker P, Brechlin P, Schindehuette J, Poser S, Wiltfang J, Otto M (2006) Beta-amyloid 1–42 and tau-protein in cerebrospinal fluid of patients with Parkinson’s disease dementia. Dement Geriatr Cogn Disord 22:200–208PubMed

Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Doring F, Trenkwalder C, Schlossmacher MG (2011) alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10:230–240PubMed

Morgan JC, Mehta SH, Sethi KD (2010) Biomarkers in Parkinson’s disease. Curr Neurol Neurosci Rep 10:423–430PubMed

Najafi B, Aminian K, Loew F, Blanc Y, Robert PA (2002) Measurement of stand-sit and sit-stand transitions using a miniature gyroscope and its application in fall risk evaluation in the elderly. IEEE Trans Biomed Eng 49:843–851PubMed

Nurmi E, Ruottinen HM, Bergman J, Haaparanta M, Solin O, Sonninen P, Rinne JO (2001) Rate of progression in Parkinson’s disease: a 6-[18F]fluoro-L-dopa PET study. Mov Disord 16:608–615PubMed

Nyhlen J, Constantinescu R, Zetterberg H (2010) Problems associated with fluid biomarkers for Parkinson’s disease. Biomarkers Med 4:671–681

Onofrj M, Thomas A, D’Andreamatteo G, Iacono D, Luciano AL, Di Rollo A, Di Mascio R, Ballone E, Di Iorio A (2002) Incidence of RBD and hallucination in patients affected by Parkinson’s disease: 8-year follow-up. Neurol Sci 23(Suppl 2):S91–S94PubMed

Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H (1999) (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194PubMed

Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM (2005) A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain 128:2665–2674PubMed

Peran P, Cherubini A, Assogna F, Piras F, Quattrocchi C, Peppe A, Celsis P, Rascol O, Demonet JF, Stefani A, Pierantozzi M, Pontieri FE, Caltagirone C, Spalletta G, Sabatini U (2010) Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain 133:3423–3433PubMed

Plotnik M, Giladi N, Hausdorff JM (2007) A new measure for quantifying the bilateral coordination of human gait: effects of aging and Parkinson’s disease. Exp Brain Res 181:561–570PubMed

Plotnik M, Giladi N, Hausdorff JM (2009) Bilateral coordination of gait and Parkinson’s disease: the effects of dual tasking. J Neurol Neurosurg Psychiatry 80:347–350PubMed

Ponsen MM, Stoffers D, Twisk JWR, Wolters EC, Berendse HW (2009) Hyposmia and executive dysfunction as predictors of future Parkinson’s disease: a prospective study. Mov Disord 24:1060–1065PubMed

Riederer P, Wuketich S (1976) Time course of nigrostriatal degeneration in Parkinson’s disease. A detailed study of influential factors in human brain amine analysis. J Neural Transm 38:277–301PubMed

Rigas G, Tzallas AT, Tsalikakis DG, Konitsiotis S, Fotiadis DI (2009) Real-time quantification of resting tremor in the Parkinson’s disease. Conf Proc IEEE Eng Med Biol Soc 1306–1309

Rojo A, Aguilar M, Garolera MT, Cubo E, Navas I, Quintana S (2003) Depression in Parkinson’s disease: clinical correlates and outcome. Parkinsonism Relat Disord 10:23–28PubMed

Ryvlin P, Broussolle E, Piollet H, Viallet F, Khalfallah Y, Chazot G (1995) Magnetic resonance imaging evidence of decreased putamenal iron content in idiopathic Parkinson’s disease. Arch Neurol 52:583–588PubMed

Sato S, Mizuno Y, Hattori N (2005) Urinary 8-hydroxyguanosine levels as a biomarker for progression of Parkinson’s disease. Neurology 64:1081–1083PubMed

Scherzer CR, Eklund AC, Morse LJ, Liao ZX, Locascio JJ, Fefer D, Schwarzschild MA, Schlossmacher MG, Hauser MA, Vance JM, Sudarsky LR, Standaert DG, Growdon JH, Jensen RV, Gullans SR (2007) Molecular markers of early Parkinson’s disease based on gene expression in blood. Proc Natl Acad Sci USA 104:955–960PubMed

Schestatsky P, Ehlers JA, Rieder CR, Gomes I (2006) Evaluation of sympathetic skin response in Parkinson’s disease. Parkinsonism Relat Disord 12:486–491PubMed

Schiesling C, Kieper N, Seidel K, Kruger R (2008) Familial Parkinson’s disease—genetics, clinical phenotype and neuropathology in relation to the common sporadic form of the disease. Neuropathol Appl Neurobiol 34:255–271PubMed

Schlesinger I, Schlesinger N (2008) Uric acid in Parkinson’s disease. Mov Disord 23:1653–1657PubMed

Schlesinger I, Benyakov O, Erikh I, Suraiya S, Schiller Y (2009) Parkinson’s disease tremor is diminished with relaxation guided imagery. Mov Disord 24:2059–2062PubMed

Schrag A, Dodel R, Spottke A, Bornschein B, Siebert U, Quinn NP (2007) Rate of clinical progression in Parkinson’s disease. A prospective study. Mov Disord 22:938–945PubMed

Schwarzschild MA, Schwid SR, Marek K, Watts A, Lang AE, Oakes D, Shoulson I, Ascherio A, and the Parkinson Study Group PRECEPT Investigators (2008) Serum urate as a predictor of clinical and radiographic progression in Parkinsons disease. Arch Neurol 65:716–723PubMed

Serrano-Duenas M, Calero B, Serrano S, Serrano M, Coronel P (2010) Psychometric attributes of the rating scale for gait evaluation in Parkinson’s disease. Mov Disord 25:2121–2127PubMed

Shaw LM, Korecka M, Clark CM, Lee VM-Y, Trojanowski JQ (2007) Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nature Rev 6:295–303

Shi M, Bradner J, Hancock AM, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Kim HM, Leverenz JB, Montine TJ, Ginghina C, Kang UJ, Cain KC, Wang Y, Aasly J, Goldstein D, Zhang J (2011) Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol 69:570–580PubMed

Shibata M, Morita Y, Shimizu T, Takahashi K, Suzuki N (2009) Cardiac parasympathetic dysfunction concurrent with cardiac sympathetic denervation in Parkinson’s disease. J Neurol Sci 276:79–83PubMed

Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355PubMed

Suzuki M, Urashima M, Oka H, Hashimoto M, Taira K (2007) Cardiac sympathetic denervation in bradykinesia-dominant Parkinson’s disease. Neuroreport 18:1867–1870PubMed

The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group (1998) Consensus report of the Working Group on: “Molecular and Biochemical Markers of Alzheimer’s Disease”. Neurobiol Aging 19:109–116

Visser JE, Voermans NC, Oude Nijhuis LB, van der Eijk M, Nijk R, Munneke M, Bloem BR (2007) Quantification of trunk rotations during turning and walking in Parkinson’s disease. Clin Neurophysiol 118:1602–1606PubMed

Waragai M, Wei J, Fujita M, Nakai M, Ho GJ, Masliah E, Akatsu H, Yamada T, Hashimoto M (2006) Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s disease. Biochem Biophys Res Commun 345:967–972PubMed

Weiss A, Herman T, Plotnik M, Brozgol M, Maidan I, Giladi N, Gurevich T, Hausdorff JM (2010) Can an accelerometer enhance the utility of the Timed Up and Go Test when evaluating patients with Parkinson’s disease? Med Eng Phys 32:119–125PubMed

Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ, for the REAL-PET Study Group (2003) Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol 54:93–101PubMed

Williams DR, Lees AJ (2005) Visual hallucinations in the diagnosis of idiopathic Parkinson’s disease: a retrospective autopsy study. Lancet Neurol 4:605–610PubMed

Wullner U, Schmitz-Hubsch T, Antony G, Fimmers R, Spottke A, Oertel WH, Deuschl G, Klockgether T, Eggert K (2007) Autonomic dysfunction in 3414 Parkinson’s disease patients enrolled in the German Network on Parkinson’s disease (KNP e.V.): the effect of ageing. Eur J Neurol 14:1405–1408PubMed

Yang YX, Wood NW, Latchman DS (2009) Molecular basis of Parkinson’s disease. Neuroreport 20:150–156PubMed

Younes-Mheni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G (2007) Peripheral blood markers of oxidative stress in Parkinson’s disease. Eur Neurol 58:78–83

Zampieri C, Salarian A, Carlson-Kuhta P, Aminian K, Nutt JG, Horak FB (2010) The instrumented timed up and go test: potential outcome measure for disease modifying therapies in Parkinson’s disease. J Neurol Neurosurg Psychiatry 81:171–176PubMed

Zetterberg H, Ruetschi U, Portelius E, Brinkmalm G, Andreasson U, Blennow K, Brinkmalm A (2008) Clinical proteomics in neurodegenerative disorders. Acta Neurol Scand 118:1–11PubMed

Zhang J, Sokal I, Peskind ER, Quinn JF, Jankovic J, Kenney C, Chung KA, Millard SP, Nutt JG, Montine TJ (2008) CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol 129:526–529PubMed

Title: Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics
Authors: Manfred Gerlach
Walter Maetzler
Karl Broich
Harald Hampel
Lucas Rems
Torsten Reum
Peter Riederer
Albrecht Stöffler
Johannes Streffer
Daniela Berg
Publication date: 01-01-2012
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 1/2012
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-011-0682-x

At a glance: The STEP trials

Springer Medicine

Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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