Biomarker Candidates of Neurodegeneration in Parkinson's Disease for the Evaluation of Disease-modifying Therapeutics

Overview

Journal J Neural Transm (Vienna)

Specialties Neurology
Physiology

Date 2011 Jul 15

PMID 21755462

Citations 28

Authors

Manfred Gerlach

Walter Maetzler

Karl Broich

Harald Hampel

Lucas Rems

Torsten Reum

Peter Riederer

Albrecht Stoffler

Johannes Streffer

Daniela Berg

Affiliations

Soon will be listed here.

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.

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References

Scherzer C, Eklund A, Morse L, Liao Z, Locascio J, Fefer D . Molecular markers of early Parkinson's disease based on gene expression in blood. Proc Natl Acad Sci U S A. 2007; 104(3):955-60. PMC: 1766335. DOI: 10.1073/pnas.0610204104. View

Aarsland D, Andersen K, Larsen J, Perry R, Wentzel-Larsen T, Lolk A . The rate of cognitive decline in Parkinson disease. Arch Neurol. 2004; 61(12):1906-11. DOI: 10.1001/archneur.61.12.1906. View

Double K, Rowe D, Carew-Jones F, Hayes M, Chan D, Blackie J . Anti-melanin antibodies are increased in sera in Parkinson's disease. Exp Neurol. 2009; 217(2):297-301. DOI: 10.1016/j.expneurol.2009.03.002. View

Johansen K, Wang L, Aasly J, White L, Matson W, Henchcliffe C . Metabolomic profiling in LRRK2-related Parkinson's disease. PLoS One. 2009; 4(10):e7551. PMC: 2761616. DOI: 10.1371/journal.pone.0007551. View

Grunblatt E, Mandel S, Jacob-Hirsch J, Zeligson S, Amariglo N, Rechavi G . 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 (Vienna). 2004; 111(12):1543-73. DOI: 10.1007/s00702-004-0212-1. View

Irizarry M, Gurol M, Raju S, Diaz-Arrastia R, Locascio J, Tennis M . Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology. 2005; 65(9):1402-8. DOI: 10.1212/01.wnl.0000183063.99107.5c. View

Halperin I, Morelli M, Korczyn A, Youdim M, Mandel S . Biomarkers for evaluation of clinical efficacy of multipotential neuroprotective drugs for Alzheimer's and Parkinson's diseases. Neurotherapeutics. 2008; 6(1):128-40. PMC: 5084261. DOI: 10.1016/j.nurt.2008.10.033. View

Wullner U, Schmitz-Hubsch T, Antony G, Fimmers R, Spottke A, Oertel W . 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. 2007; 14(12):1405-8. DOI: 10.1111/j.1468-1331.2007.01982.x. View

Graham J, Paley M, Grunewald R, Hoggard N, Griffiths P . Brain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence. Brain. 2000; 123 Pt 12:2423-31. DOI: 10.1093/brain/123.12.2423. View

10.

Rojo A, Aguilar M, Garolera M, Cubo E, Navas I, Quintana S . Depression in Parkinson's disease: clinical correlates and outcome. Parkinsonism Relat Disord. 2003; 10(1):23-8. DOI: 10.1016/s1353-8020(03)00067-1. View

11.

Ponsen M, Stoffers D, Twisk J, Wolters E, Berendse H . Hyposmia and executive dysfunction as predictors of future Parkinson's disease: a prospective study. Mov Disord. 2009; 24(7):1060-5. DOI: 10.1002/mds.22534. View

12.

. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69(3):89-95. DOI: 10.1067/mcp.2001.113989. View

13.

Carpenter M, Allum J, Honegger F, Adkin A, Bloem B . Postural abnormalities to multidirectional stance perturbations in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004; 75(9):1245-54. PMC: 1739252. DOI: 10.1136/jnnp.2003.021147. View

14.

Mancini M, Zampieri C, Carlson-Kuhta P, Chiari L, Horak F . Anticipatory postural adjustments prior to step initiation are hypometric in untreated Parkinson's disease: an accelerometer-based approach. Eur J Neurol. 2009; 16(9):1028-34. PMC: 2840629. DOI: 10.1111/j.1468-1331.2009.02641.x. View

15.

Klein C, Schneider S, Lang A . Hereditary parkinsonism: Parkinson disease look-alikes--an algorithm for clinicians to "PARK" genes and beyond. Mov Disord. 2009; 24(14):2042-58. DOI: 10.1002/mds.22675. View

16.

Waragai M, Wei J, Fujita M, Nakai M, Ho G, Masliah E . Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson's disease. Biochem Biophys Res Commun. 2006; 345(3):967-72. DOI: 10.1016/j.bbrc.2006.05.011. View

17.

Maetzler W, Liepelt I, Reimold M, Reischl G, Solbach C, Becker C . Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics. Neurobiol Dis. 2009; 34(1):107-12. DOI: 10.1016/j.nbd.2008.12.008. View

18.

El-Agnaf O, Salem S, Paleologou K, Curran M, Gibson M, Court J . Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J. 2006; 20(3):419-25. DOI: 10.1096/fj.03-1449com. View

19.

. Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease". The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. Neurobiol Aging. 1998; 19(2):109-16. View

20.

Braak H, Braak E, Yilmazer D, Schultz C, de Vos R, Jansen E . Nigral and extranigral pathology in Parkinson's disease. J Neural Transm Suppl. 1995; 46:15-31. View