• Please log in or register to access this feature.

Review

You have free access to this content

Biomarkers for trials of neuroprotection in Parkinson's disease

  1. Pankaj A. Agarwal MD, DNB, DM1,
  2. A. Jon Stoessl CM, MD, FRCPC1,2,*

Article first published online: 24 AUG 2012

DOI: 10.1002/mds.25065

Issue

Movement Disorders

Movement Disorders

Special Issue: The Vatican Conference on Neuroprotection in Parkinson's Disease

Volume 28, Issue 1, pages 71–85, January 2013

Additional Information

How to Cite

Agarwal, P. A. and Stoessl, A. J. (2013), Biomarkers for trials of neuroprotection in Parkinson's disease. Mov. Disord., 28: 71–85. doi: 10.1002/mds.25065

Author Information

  1. 1

    Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

  2. 2

    Vancouver Costal Health, Vancouver, British Columbia, Canada

*Correspondence to: A. Jon Stoessl, Pacific Parkinson's Research Center, University of British Columbia, Vancouver Hospital and Health Sciences Center, Purdy Pavilion, 2221Wesbrook Mall, Vancouver, British Columbia, Canada V6T 2B5; jstoessl@mail.ubc.ca

  1. Funding agencies: The work of A.J.S. is supported by the Canadian Institutes of Health Research, the Michael J. Fox Foundation, the Pacific Alzheimer Research Foundation, and the Canada Research Chairs program.

  2. Relevant conflicts of interest/financial disclosure: Nothing to report.

  3. Full financial disclosures and author roles may be found in the online version of this article.

Publication History

  1. Issue published online: 6 FEB 2013
  2. Article first published online: 24 AUG 2012
  3. Manuscript Accepted: 23 APR 2012
  4. Manuscript Revised: 19 APR 2012
  5. Manuscript Received: 18 JAN 2012

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (2548K)

References

  • 1
    de Rijk MC, Launer LJ, Berger K, Breteler MMB, Dartigues JF, Baldereschi M et al. Prevalence of Parkinson's disease in Europe: a collaborative study of population-based cohorts. Neurology 2000;54:S21–S23.
  • 2
    Atkinson AJ, Colburn WA, DeGruttola VG, et al. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89–95.
  • 3
    Bernheim H, Birkmaye W, Hornykie O, Jellinge K, Seitelbe F. Brain dopamine and syndromes of Parkinson and Huntington. Clinical, morphological, and neurochemical correlations. J Neurol Sci 1973;20:415–455.
  • 4
    Fearnley JM, Lees AJ. Aging and Parkinson's disease: substantia nigra regional selectivity. Brain 1991;114:2283–2301.
  • 5
    Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson's disease. N Engl J Med 2004;351:2498–2508.
  • 6
    Meara J, Bhowmick BK, Hobson P. Accuracy of diagnosis in patients with presumed Parkinson's disease. Age Ageing 1999;28:99–102.
  • 7
    Snow BJ, Tooyama I, McGeer EG, et al. Human positron emission tomographic [18F]fluorodopa studies correlate with dopamine cell counts and levels. Ann Neurol 1993;34:324–330.
    Direct Link:
  • 8
    Pate BD, Kawamata T, Yamada T, et al. Correlation of striatal fluorodopa uptake in the MPTP monkey with dopaminergic indices. Ann Neurol 1993;34:331–338.
    Direct Link:
  • 9
    Vingerhoets FJ, Schulzer M, Calne DB, Snow BJ. Which clinical sign of Parkinson's disease best reflects the nigrostriatal lesion? Ann Neurol 1997;41:58–64.
    Direct Link:
  • 10
    Martin WRW, Palmer MR, Patlak CS, Calne DB. Nigrostriatal function in humans studied with positron emission tomography. Ann Neurol 1989;26:535–542.
    Direct Link:
  • 11
    Sossi V, Fuente-Fernandez R, Holden JE, et al. Increase in dopamine turnover occurs early in Parkinson's disease: evidence from a new modeling approach to PET 18 F-fluorodopa data. J Cereb Blood Flow Metab 2002;22:232–239.
  • 12
    Doudet DJ, Chan GL, Holden JE, et al. 6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys. Synapse 1998;29:225–232.
    Direct Link:
  • 13
    DeJesus OT, Endres CJ, Shelton SE, Nickles RJ, Holden JE. Evaluation of fluorinated m-tyrosine analogs as PET imaging agents of dopamine nerve terminals: comparison with 6-fluoroDOPA. J Nucl Med 1997;38:630–636.
  • 14
    Doudet DJ, Chan GLY, Jivan S, et al. Evaluation of dopaminergic presynaptic integrity: 6-[18F]fluoro-L-dopa versus 6-[18F]fluoro-L-m-tyrosine. J Cereb Blood Flow Metab 1999;19:278–287.
  • 15
    Jordan S, Eberling JL, Bankiewicz KS, et al. 6-[18F]fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates. Brain Res 1997;750:276.
  • 16
    Christine CW, Starr A, Larson PS, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 2009;73:1662–1669.
  • 17
    Gallagher CL, Christian BT, Holden JE, et al. A within-subject comparison of 6-[18F]fluoro-m-tyrosine and 6-[18F]fluoro-L-dopa in Parkinson's disease. Mov Disord 2011;26:2032–2038.
    Direct Link:
  • 18
    Moore RY, Whone AL, McGowan S, Brooks DJ. Monoamine neuron innervation of the normal human brain: an F-18-DOPA PET study. Brain Res 2003;982:137–145.
  • 19
    Pavese N, Simpson BS, Metta V, Ramlackhansingh A, Chaudhuri KR, Brooks DJ. [(18)F]FDOPA uptake in the raphe nuclei complex reflects serotonin transporter availability. A combined [(18)F]FDOPA and [(11)C]DASB PET study in Parkinson's disease. Neuroimage 2012;59:1080–1084.
  • 20
    Hersch SM, Yi H, Heilman CJ, Edwards RH, Levey AI. Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra. J Comp Neurol 1997;388:211–227.
    Direct Link:
  • 21
    Nirenberg MJ, Chan J, Liu YJ, Edwards RH, Pickel VM. Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons: potential sites for somatodendritic storage and release of dopamine. J Neurosci 1996;16:4135–4145.
  • 22
    Bezard E, Dovero S, Prunier C, et al. Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease. J Neurosci 2001;21:6853–6861.
  • 23
    Pirker W. Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it? Mov Disord 2003;18:S43–SS51.
    Direct Link:
  • 24
    Seibyl JP, Marek KL, Quinlan D, et al. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol 1995;38:589–598.
    Direct Link:
  • 25
    Nurmi E, Bergman J, Eskola O, et al. Reproducibility and effect of levodopa on dopamine transporter function measurements: a [F-18]CFT PET study. J Cereb Blood Flow Metab 2000;20:1604–1609.
  • 26
    Seibyl JP, Marek K, Sheff K, et al. Test/retest reproducibility of iodine-123-β CIT SPECT brain measurement of dopamine transporters in Parkinson's patients. J Nucl Med 1997;38:1453–1459.
  • 27
    Volkow ND, Ding YS, Fowler JS, et al. A new PET ligand for the dopamine transporter: studies in the human brain. J Nucl Med 1995;36:2162–2168.
  • 28
    Vanderborght TM, Sima AAF, Kilbourn MR, Desmond TJ, Kuhl DE, Frey KA. [H-3]methoxytetrabenazine: a high specific activity ligand for estimating monoaminergic neuronal integrity. Neuroscience 1995;68:955–962.
  • 29
    Vanderborght T, Kilbourn M, Desmond T, Kuhl D, Frey K. The vesicular monoamine transporter is not regulated by dopaminergic drug treatments. Eur J Pharmacol 1995;294:577–583.
  • 30
    Wilson JM, Kish SJ. The vesicular monoamine transporter, in contrast to the dopamine transporter, is not altered by chronic cocaine self-administration in the rat. J Neurosci 1996;16:3507–3510.
  • 31
    de la Fuente-Fernandez R, Furtado S, Guttman M, et al. VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET. Synapse 2003;49:20–28.
    Direct Link:
  • 32
    Fuente-Fernandez R, Sossi V, McCormick S, Schulzer M, Ruth TJ, Stoessl AJ. Visualizing vesicular dopamine dynamics in Parkinson's disease. Synapse 2009;63:713–716.
    Direct Link:
  • 33
    Boileau I, Rusjan P, Houle S, et al. Increased vesicular monoamine transporter binding during early abstinence in human methamphetamine users: is VMAT2 a stable dopamine neuron biomarker? J Neurosci 2008;28:9850–9856.
  • 34
    Tong JC, Wilson AA, Boileau I, Houle S, Kish SJ. Dopamine modulating drugs influence striatal (+)-[(11)C]DTBZ binding in rats: VMAT2 binding is sensitive to changes in vesicular dopamine concentration. Synapse 2008;62:873–876.
    Direct Link:
  • 35
    Lee CS, Samii A, Sossi V, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease. Ann Neurol 2000;47:493–503.
    Direct Link:
  • 36
    Marek K, Seibyl J, Shoulson I, et al. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 2002;287:1653–1661.
  • 37
    Volkow ND, Fowler JS, Wang GJ, et al. Decreased dopamine transporters with age in healthy human subjects. Ann Neurol 1994;36:237–239.
    Direct Link:
  • 38
    de Paulis T. The discovery of epidepride and its analogs as high-affinity radioligands for imaging extrastriatal dopamine D(2) receptors in human brain. Curr Pharm Des 2003;9:673–696.
  • 39
    Pinborg LH, Videbaek C, Ziebell M, et al. [I-123]epidepride binding to cerebellar dopamine D-2/D-3 receptors is displaceable: implications for the use of cerebellum as a reference region. Neuroimage 2007;34:1450–1453.
  • 40
    Antonini A, Schwarz J, Oertel WH, Pogarell O, Leenders KL. Long-term changes of striatal dopamine D-2 receptors in patients with Parkinson's disease: a study with positron emission tomography and [C-11]raclopride. Mov Disord 1997;12:33–38.
    Direct Link:
  • 41
    Kaasinen V, Ruottinen HM, Nagren K, Lehikoinen P, Oikonen V, Rinne JO. Upregulation of putaminal dopamine D2 receptors in early Parkinson's disease: a comparative PET study with [11C]raclopride and [11C]N-methylspiperone. J Nucl Med 2000;41:65–70.
  • 42
    Thobois S, Vingerhoets F, Fraix V, et al. Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease: a positron emission tomographic study. Arch Neurol 2004;61:1705–1709.
  • 43
    Rinne JO, Laihinen A, Nagren K, et al. PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease. J Neurosci Res 1990;27:494–499.
    Direct Link:
  • 44
    Ma YL, Tang CK, Spetsieris PG, Dhawan V, Eidelberg D. Abnormal metabolic network activity in Parkinson's disease: test-retest reproducibility. J Cereb Blood Flow Metab 2007;27:597–605.
  • 45
    Eckert T, Van Laere K, Tang CK, et al. Quantification of Parkinson's disease-related network expression with ECD SPECT. Eur J Nucl Med Mol Imaging 2007;34:496–501.
  • 46
    Asanuma K, Tang C, Ma Y, et al. Network modulation in the treatment of Parkinson's disease. Brain 2006;129:2667–2678.
  • 47
    Eckert T, Eidelberg D. Neuroimaging and therapeutics in movement disorders. NeuroRx 2005;2:361–371.
  • 48
    Ma Y, Huang C, Dyke JP, et al. Parkinson's disease spatial covariance pattern: noninvasive quantification with perfusion MRI. J Cereb Blood Flow Metab 2010;30:505–509.
  • 49
    Calne DB, Langston JW, Martin WR, et al. Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease. Nature 1985;317:246–248.
  • 50
    Piccini P, Burn DJ, Ceravolo R, Maraganore DM, Brooks DJ. The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins. Ann Neurol 1999;45:577–582.
    Direct Link:
  • 51
    Adams JR, van Netten H, Schulzer M, et al. PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation. Brain 2005;128:2777–2785.
  • 52
    Nandhagopal R, Mak E, Schulzer M, et al. Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study. Neurology 2008;71:1790–1795.
  • 53
    Sossi V, Fuente-Fernandez R, Nandhagopal R, et al. Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. Mov Disord 2010;25:2717–2723.
    Direct Link:
  • 54
    Khan NL, Scherfler C, Graham E, et al. Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation. Neurology 2005;64:134–136.
  • 55
    Khan NL, Valente EM, Bentivoglio AR, et al. Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an 18F-dopa PET study. Ann Neurol 2002;52:849–853.
    Direct Link:
  • 56
    Ponsen MM, Stoffers D, Booij J, Eck-Smit BL, Wolters EC, Berendse HW. Idiopathic hyposmia as a preclinical sign of Parkinson's disease. Ann Neurol 2004;56:173–181.
    Direct Link:
  • 57
    Berg D, Roggendorf W, Schroder U, et al. Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 2002;59:999–1005.
  • 58
    Sommer U, Hummel T, Cormann K, et al. Detection of presymptomatic Parkinson's disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 2004;19:1196–1202.
    Direct Link:
  • 59
    Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 2009;72:1296–1300.
  • 60
    Albin RL, Koeppe RA, Chervin RD, et al. Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 2000;55:1410–1412.
  • 61
    Iranzo A, Valldeoriola F, Lomena F, et al. Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2011;10:797–805.
  • 62
    Stockner H, Iranzo A, Seppi K, et al. Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder. Mov Disord 2009;24:1906–1909.
    Direct Link:
  • 63
    Scherfler C, Frauscher B, Schocke M, et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol 2011;69:400–407.
    Direct Link:
  • 64
    Unger MM, Belke M, Menzler K, et al. Diffusion Tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep 2010;33:767–773.
  • 65
    Schneider SA, Edwards MJ, Mir P, et al. Patients with adult-onset dystonic tremor resembling parkinsonian tremor have scans without evidence of dopaminergic deficit (SWEDDs). Mov Disord 2007;22:2210–2215.
    Direct Link:
  • 66
    Silveira-Moriyama L, Schwingenschuh P, O'Donnell A, et al. Olfaction in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDDs). J Neurol Neurosurg Psychiatry 2009;80:744–748.
  • 67
    Schwingenschuh P, Ruge D, Edwards MJ, et al. Distinguishing SWEDDs patients with asymmetric resting tremor from Parkinson's disease: a clinical and electrophysiological study. Mov Disord 2010;25:560–569.
    Direct Link:
  • 68
    Marshall VL, Patterson J, Hadley DM, Grosset KA, Grosset DG. Two-year follow-up in 150 consecutive cases with normal dopamine transporter imaging. Nucl Med Commun 2006;27:933–937.
  • 69
    Marshall VL, Patterson J, Hadley DM, Grosset KA, Grosset DG. Successful antiparkinsonian medication withdrawal in patients with parkinsonism and normal FP-CIT SPECT. Mov Disord 2006;21:2247–2250.
    Direct Link:
  • 70
    Gibb WR, Lees AJ. Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. J Neurol Neurosurg Psychiatry 1991;54:388–396.
  • 71
    Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. N Engl J Med 1988;318:876–880.
  • 72
    Antonini A, Leenders KL, Vontobel P, et al. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease. Brain 1997;120:2187–2195.
  • 73
    Eckert T, Barnes A, Dhawan V, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005;26:912–921.
  • 74
    Eckert T, Van Laere K, Tang CK, et al. Quantification of Parkinson's disease-related network expression with ECD SPECT. Eur J Nucl Med Mol Imaging 2007;34:496–501.
  • 75
    Tang CC, Poston KL, Dhawan V, Eidelberg D. Abnormalities in metabolic network activity precede the onset of motor symptoms in Parkinson's disease. J Neurosci 2010;30:1049–1056.
  • 76
    Eidelberg D, Takikawa S, Moeller JR, et al. Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease. Ann Neurol 1993;33:518–527.
    Direct Link:
  • 77
    Antonini A, Kazumata K, Feigin A, et al. Differential diagnosis of parkinsonism with [F-18]fluorodeoxyglucose and PET. Mov Disord 1998;13:268–274.
    Direct Link:
  • 78
    Tang CC, Poston KL, Eckert T, et al. Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol 2010;9:149–158.
  • 79
    Benamer HTS, Patterson J, Grosset DG, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [I-123]-FP-CIT SPECT imaging: the [I-123]-FP-CIT study group. Mov Disord 2000;15:503–510.
    Direct Link:
  • 80
    Benaderette S, Zanotti Fregonara P, Apartis E, et al. Psychogenic parkinsonism: a combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy. Mov Disord 2006;21:310–317.
    Direct Link:
  • 81
    Felicio AC, Godeiro C, Moriyama TS, et al. Degenerative parkinsonism in patients with psychogenic parkinsonism: a dopamine transporter imaging study. Clin Neurol Neurosurg 2010;112:282–285.
  • 82
    Yoshita M. Differentiation of idiopathic Parkinson's disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 1998;155:60–67.
  • 83
    Bohnen NI, Albin RL, Koeppe RA, et al. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J Cereb Blood Flow Metab 2006;26:1198–1212.
  • 84
    Marek KL, Seibyl JP, Zoghbi SS, et al. [I-123] β-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease. Neurology 1996;46:231–237.
  • 85
    Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study. Brain 2009;132:2970–2979.
  • 86
    Bruck A, Aalto S, Rauhala E, Bergman J, Marttila R, Rinne JO. A follow-up study on 6-[18F]fluoro-L-dopa uptake in early Parkinson's disease shows nonlinear progression in the putamen. Mov Disord 2009;24:1009–1015.
    Direct Link:
  • 87
    Tatton WG, Chalmers-Redman R, Brown D, Tatton N. Apoptosis in Parkinson's disease: signals for neuronal degradation. Ann Neurol 2003;53:S61–S70.
    Direct Link:
  • 88
    Muchowskil PJ. Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron 2002;35:9–12.
  • 89
    Schapira AHV, Gu M, Taanman JW, et al. Mitochondria in the etiology and pathogenesis of Parkinson's disease. Ann Neurol 1998;44:S89–S98.
  • 90
    Nurmi E, Bergman J, Eskola O, et al. Progression of dopaminergic hypofunction in striatal subregions in Parkinson's disease using [F-18]CFT PET. Synapse 2003;48:109–115.
    Direct Link:
  • 91
    Schulzer M, Lee CS, Mak EK, Vingerhoets FJG, Calne DB. A mathematical model of pathogenesis in idiopathic parkinsonism. Brain 1994;117:509–516.
  • 92
    Hilker R, Schweitzer K, Coburger S, et al. Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity. Arch Neurol 2005;62:378–382.
  • 93
    Morrish PK, Rakshi JS, Bailey DL, Sawle GV, Brooks DJ. Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [F-18] dopa PET. J Neurol Neurosurg Psychiatry 1998;64:314–319.
  • 94
    Fuente-Fernandez R, Schulzer M, Kuramoto L, et al. Age-specific progression of nigrostriatal dysfunction in Parkinson's disease. Ann Neurol 2011;69:803–810.
    Direct Link:
  • 95
    Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease. Brain 2011;134:3290–3298.
  • 96
    Huang CR, Tang CK, Feigin A, et al. Changes in network activity with the progression of Parkinson's disease. Brain 2007;130:1834–1846.
  • 97
    Trost M, Su S, Su P, et al. Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease. Neuroimage 2006;31:301–307.
  • 98
    Parkinson Study Group. A randomized controlled trial comparing pramipexole with levodopa in early Parkinson's disease: design and methods of the CALM-PD Study. Parkinson Study Group. Clin Neuropharmacol 2000;23:34–44.
  • 99
    Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 2003;54:93–101.
    Direct Link:
  • 100
    Fahn S. Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs later L-DOPA. Arch Neurol 1999;56:529–535.
  • 101
    Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001;344:710–719.
  • 102
    Nakamura T, Dhawan V, Chaly T, et al. Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease. Ann Neurol 2001;50:181–187.
    Direct Link:
  • 103
    Olanow CW, Goetz CG, Kordower JH, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 2003;54:403–414.
    Direct Link:
  • 104
    Stoessl AJ. Agonizing over dopaminergic replacement therapy—lessons from animal models of Parkinson's disease. Exp Neurol 2003;183:1–3.
  • 105
    Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003;9:589–595.
  • 106
    Lang AE, Gill S, Patel NK, et al. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006;59:459–466.
    Direct Link:
  • 107
    Lang AE, Obeso JA. Time to move beyond nigrostriatal dopamine deficiency in Parkinson's disease. Ann Neurol 2004;55:761–765.
    Direct Link:
  • 108
    Piccini P, Lindvall O, Bjorklund A, et al. Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts. Ann Neurol 2000;48:689–695.
    Direct Link:
  • 109
    Kaplitt MG, Feigin A, Tang C, et al. Safety and tolerability of AAV-GAD gene therapy for Parkinson's disease: an open label, phase I trial. Lancet 2007;369:2097–2105.
  • 110
    Feigin A, Kaplitt MG, Tang C, et al. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease. Proc Natl Acad Sci U S A 2007;104:19559–19564.
  • 111
    Vaillancourt DE, Spraker MB, Prodoehl J, et al. High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology 2009;72:1378–1384.
  • 112
    Zhan W, Kang GA, Glass GA, et al. Regional alterations of brain microstructure in parkinson's disease using diffusion tensor imaging. Mov Disord 2012;27:90–97.
    Direct Link:
  • 113
    Martin WRW, Wieler M, Gee M. Midbrain iron content in early Parkinson disease: a potential biomarker of disease status. Neurology 2008;70:1411–1417.
  • 114
    Peran P, Cherubini A, Assogna F, et al. Magnetic resonance imaging markers of Parkinson's disease nigrostriatal signature. Brain 2010;133:3423–3433.
  • 115
    Becker G, Seufert J, Bogdahn U, Reichmann H, Reiners K. Degeneration of substantia-nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography. Neurology 1995;45:182–184.
  • 116
    Berg D, Becker G, Zeiler B, et al. Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 1999;53:1026–1031.
  • 117
    Berg D, Metz B, Reiners K, Naumann M, Becker G. Five-year follow-up study of hyperechogenicity of the substantia nigra in Parkinson's disease. Mov Disord 2005;20:383–385.
    Direct Link:
  • 118
    Ravina B, Eidelberg D, Ahlskog JE, et al. The role of radiotracer imaging in Parkinson disease. Neurology 2005;64:208–215.
  • 119
    Stoessl AJ. Functional imaging studies of non-motoric manifestations of Parkinson's Disease. Parkinsonism Relat Disord 2009;15( Suppl 3):S13–S16.
  • 120
    Hong Z, Shi M, Chung KA, et al. DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 2010;133:713–726.
  • 121
    Shi M, Bradner J, Hancock AM, et al. Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol 2011;69:570–580.
    Direct Link:
  • 122
    Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Doring F, Trenkwalder C, Schlossmacher MG. alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 2011;10:230–240.
  • 123
    El Agnaf OMA, Salem SA, Paleologou KE, et al. Detection of oligomeric forms of α-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J 2006;20:419–425.
  • 124
    Tokuda T, Qureshi MM, Ardah MT, et al. Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 2010;75:1766–1772.
  • 125
    Hoepken HH, Gispert S, Azizov M, et al. Parkinson patient fibroblasts show increased α-synuclein expression. Exp Neurol 2008;212:307–313.
  • 126
    Shi M, Furay AR, Sossi V, Aasly JO, et al. DJ-1 and aSYN in LRRK2 CSF do not correlate with striatal dopaminergic function. Neurobiol Aging 2012;33:836.e5–7.
  • 127
    Montine TJ, Shi M, Quinn JF, et al. CSF A beta(42) and tau in Parkinson's disease with cognitive impairment. Mov Disord 2010;25:2682–2685.
    Direct Link:
  • 128
    Compta Y, Ezquerra M, Munoz E, et al. High cerebrospinal tau levels are associated with the rs242557 tau gene variant and low cerebrospinal beta-amyloid in Parkinson disease. Neurosci Lett 2011;487:169–173.
  • 129
    Aasly JO, Shi M, Sossi V, et al. Cerebrospinal fluid amyloid ß and tau in LRRK2 mutation carriers. Neurology 2012;78:55–61.
  • 130
    Chen-Plotkin AS, Hu WT, Siderowf A, et al. Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease. Ann Neurol 2011;69:655–663.
    Direct Link:
  • 131
    Zhang J, Sokal I, Peskind ER, et al. CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol 2008;129:526–529.
  • 132
    Parnetti L, Chiasserini D, Bellomo G, et al. Cerebrospinal fluid tau/alpha-synuclein ratio in Parkinson's disease and degenerative dementias. Mov Disord 2011;26:1428–1435.
    Direct Link:
  • 133
    Weisskopf MG, O'Reilly E, Chen H, Schwarzschild MA, Ascherio A. Plasma urate and risk of Parkinson's disease. Am J Epidemiol 2007;166:561–567.
  • 134
    Schlesinger I, Schlesinger N. Uric acid in Parkinson's disease. Mov Disord 2008;23:1653–1657.
    Direct Link:
  • 135
    Schwarzschild MA, Schwid SR, Marek K, et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol 2008;65:716–723.
  • 136
    Ascherio A, Lewitt PA, Xu K, et al. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol 2009;66:1460–1468.
  • 137
    Bogdanov M, Matson WR, Wang L, et al. Metabolomic profiling to develop blood biomarkers for Parkinson's disease. Brain 2008;131:389–396.
  • 138
    Schwarzschild MA, Marek K, Eberly S, et al. Serum urate and probability of dopaminergic deficit in early “Parkinson's disease”. Mov Disord 2011;26:1864–1868.
    Direct Link:
  • 139
    Sato S, Mizuno Y, Hattori N. Urinary 8-hydroxydeoxyguanosine levels as a biomarker for progression of Parkinson disease. Neurology 2005;64:1081–1083.
  • 140
    Ihara Y, Chuda M, Kuroda S, Hayabara T. Hydroxyl radical and superoxide dismutase in blood of patients with Parkinson's disease: relationship to clinical data. J Neurol Sci 1999;170:90–95.
  • 141
    Younes-Mhenni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G. Peripheral blood markers of oxidative stress in Parkinson's disease. Eur Neurol 2007;58:78–83.
  • 142
    Sohmiya M, Tanaka M, Tak NW, et al. Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson's disease. J Neurol Sci 2004;223:161–166.
  • 143
    Isobe C, Murata T, Sato C, Terayama Y. Increase of oxidized/total coenzyme Q-10 ratio in cerebrospinal fluid in patients with Parkinson's disease. J Clin Neurosci 2007;14:340–343.
  • 144
    Ilic TV, Jovanovic M, Jovicic A, Tomovic M. Oxidative stress indicators are elevated in de novo Parkinson's disease patients. Funct Neurol 1999;14:141–147.
  • 145
    Chen H, O'Reilly EJ, Schwarzschild MA, Ascherio A. Peripheral inflammatory biomarkers and risk of Parkinson's disease. Am J Epidemiol 2008;167:90–95.
  • 146
    Rentzos M, Nikolaou C, Andreadou E, et al. Circulating interleukin-10 and interleukin-12 in Parkinson's disease. Acta Neurol Scand 2009;119:332–337.
    Direct Link:
  • 147
    Moran LB, Graeber MB. Pathways of Parkinson's disease. Neuropathol Appl Neurobiol 2008;34:15.
  • 148
    Sutherland GT, Matigian NA, Chalk AM, et al. A cross-study transcriptional analysis of Parkinson's disease. PLoS One 2009;4:e4955.
  • 149
    Grünblatt E, Zehetmayer S, Jacob CP, Müller T, Jost WH, Riederer P. Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease. J Neural Transm 2010;117:1387–1393.
  • 150
    Licker V, Kövari E, Hochstrasser DF, Burkhard PR. Proteomics in human Parkinson's disease research. J Proteomics 2009;73:10–29.
  • 151
    Andreasen N, Minthon L, Clarberg A, et al. Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. Neurology 1999;53:1488–1494.
  • 152
    Jin JH, Hulette C, Wang Y, et al. Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Mol Cell Proteomics 2006;5:1193–1204.
  • 153
    Pan S, Rush J, Peskind ER, et al. Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform. J Proteome Res 2008;7:720–730.
  • 154
    Li YH, Wang JA, Zheng XL, et al. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry combined with magnetic beads for detecting serum protein biomarkers in Parkinson's disease. Eur Neurol 2011;65:105–111.
  • 155
    Zhao X, Xiao WZ, Pu XP, Zhong LJ. Proteome analysis of the sera from Chinese Parkinson's disease patients. Neurosci Lett 2010;479:175–179.
  • 156
    Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol 2004;22:245–252.
  • 157
    Ahmed SSSJ, Santosh W, Kumar S, Christlet HTT. Metabolic profiling of Parkinson's disease: evidence of biomarker from gene expression analysis and rapid neural network detection. J Biomed Sci 2009;16.
  • 158
    Johansen KK, Wang L, Aasly JO, et al. Metabolomic profiling in LRRK2-related Parkinson's disease. Plos One 2009;4:e7551.
  • 159
    Marek K, Jennings D, Lasch S, et al. The Parkinson Progression Marker Initiative (PPMI). Prog Neurobiol 2011;95:629–635.
  • 160
    Stoessl AJ, Martin WW, McKeown MJ, Sossi V. Advances in imaging in Parkinson's disease. Lancet Neurol 2011;10:987–1001.
  • 161
    Eckert T, Tong C, Eidelberg D. Assessment of the progression of Parkinson's disease: a metabolic network approach. Lancet Neurol 2007;6:926–932.
View Full Article (HTML) Get PDF (2548K)