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Aktuelle Neurologie 2011; 38(04): 203-210
DOI: 10.1055/s-0031-1283117
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Liquordiagnostik bei der Parkinsonkrankheit mit und ohne Demenz und der Demenz mit Lewy-Körpern

Analysis of Cerebrospinal Fluid Proteins in the Diagnosis of Parkinson’s Disease, Parkinson Dementia and Dementia with Lewy Bodies
C. Weinrich
1   Universitätsmedizin Göttingen, Abteilung für klinische Neurophysiologie, Göttingen
,
A. Wrede
2   Georg-August Universität Göttingen, Abteilung Neuropathologie, Göttingen
,
B. Mollenhauer
3   Paracelsus-Elena-Klinik, Kassel und Georg-August-Universität Göttingen, Göttingen
› Author Affiliations
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Publication History

Publication Date:
18 July 2011 (online)

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Zusammenfassung

Aufgrund der demografischen Entwicklung und der alternden Bevölkerung gewinnen neurodegenerative Erkrankungen, wie die Demenzerkrankungen oder die Parkinson-Krankheit (Parkinson disease; PD) zunehmend an Bedeutung. Bislang beruht die Diagnose der meisten neurodegenerativen Erkrankungen auf klinischen Kriterien und der Verlaufsbeobachtung, sodass die Entwicklung objektiver Biomarker für die Früh- und Differenzialdiagnose dieser Erkrankungen ein aktuelles und relevantes Thema ist. Nuklearmedizinische Verfahren wie die Rezeptorszintigrafie der Dopamintransporter mit Einzel-Photonen-Emissions-Tomografie (SPECT) können dazu beitragen die Diagnose und Differenzialdiagnose der Parkinson-Krankheit und anderer Parkinson-Syndrome zu erleichtern oder eine Demenz mit Lewy-Körpern (dementia with Lewy bodies, DLB) von einer Alzheimer-Demenz (Alzheimer’s disease, AD) abzugrenzen. Für die Routinediagnostik werden kostengünstige und möglichst einfach zu bestimmende Biomarker mit hoher Sensitivität und Spezifität benötigt. Wie für die Diagnostik der Alzheimer-Demenz bereits etabliert, stellt die Analyse spezifischer Liquorproteine ein interessantes und vielversprechendes Verfahren dar, um neurodegenerative Krankheitsprozesse detektieren und deren Verlauf bestimmen zu können. Ziel dieses Artikels ist es, einen Überblick über den aktuellen Wissensstand zu Biomarkern im Liquor cerebrospinalis bei Parkinson-Krankheit mit und ohne Demenz und der Demenz mit Lewy-Körpern zu geben.

Abstract

With an ageing population neurodegenerative diseases like dementia and Parkinson’s disease are becoming more prevalent. To date the clinical diagnosis of neurodegenerative diseases is based on clinical criteria and clinical follow-up observations. For this reason there is a need to develop objective biological markers to establish an early and differential diagnosis in this field. Receptor imaging techniques of dopamine transporters with single photon emission tomography (SPECT) may contribute to the differential diagnosis of Parkinson syndromes or to distinguish dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD). For routine diagnosis a biological marker must be cheap, easy to detect and validated in terms of sensitivity and specificity. As already established for the diagnosis of AD, the analysis of specific CSF proteins might become an important diagnostic tool for other neurodegenerative diseases. The aim of this article is to give an overview of the current findings in the field of CSF biomarkers in Parkinson’s disease, Parkinson dementia and dementia with Lewy bodies.

Schlüsselwörter

Liquordiagnostik - Morbus Parkinson - Parkinson-Demenz - Demenz mit Lewy-Körpern

Keywords

analysis of cerebrospinal fluid proteins - Parkinson’s disease - Parkinson dementia - dementia with Lewy bodies
 

  • Literatur

  • 1 Dubois B, Feldman HH, Jacova C et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007; 6: 734-746
    CrossrefPubMedGoogle Scholar
  • 2 Glenner GG, Wong CW, Quaranta V et al. The amyloid deposits in Alzheimer’s disease: their nature and pathogenesis. Appl Pathol 1984; 2: 357-369
    PubMedGoogle Scholar
  • 3 Seubert P, Vigo-Pelfrey C, Esch F et al. Isolation and quantification of soluble Alzheimer’s beta-peptide from biological fluids. Nature 1992; 359: 325-327
    CrossrefPubMedGoogle Scholar
  • 4 Motter R, Vigo-Pelfrey C, Kholodenko D et al. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 1995; 38: 643-648
    CrossrefPubMedGoogle Scholar
  • 5 Hulstaert F, Blennow K, Ivanoiu A et al. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology 1999; 52: 1555-1562
    CrossrefPubMedGoogle Scholar
  • 6 Fagan AM, Mintun MA, Mach RH et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol 2006; 59: 512-519
    CrossrefPubMedGoogle Scholar
  • 7 Grundke-Iqbal I, Iqbal K, Quinlan M et al. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 1986; 261: 6084-6089
    PubMedGoogle Scholar
  • 8 Cleveland DW, Spiegelman BM, Kirschner MW. Conservation of microtubule associated proteins. Isolation and characterization of tau and the high molecular weight microtubule associated protein from chicken brain and from mouse fibroblasts and comparison to the corresponding mammalian brain proteins. J Biol Chem 1979; 254: 12670-12678
    PubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Blennow K, Wallin A, Agren H et al. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?. Mol Chem Neuropathol 1995; 26: 231-245
    CrossrefPubMedGoogle Scholar
  • 11 McKeith IG, Dickson DW, Lowe J et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005; 65: 1863-1872
    CrossrefPubMedGoogle Scholar
  • 12 McKeith I, Fairbairn A, Perry R et al. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ 1992; 305: 673-678
    CrossrefPubMedGoogle Scholar
  • 13 McKeith IG, Galasko D, Kosaka K et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996; 47: 1113-1124
    CrossrefPubMedGoogle Scholar
  • 14 Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson’s disease. Brain Pathol 20: 633-639
    PubMedGoogle Scholar
  • 15 Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. J Neurol Sci 289: 18-22
    PubMedGoogle Scholar
  • 16 Hughes AJ, Daniel SE, Kilford L et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-184
    CrossrefPubMedGoogle Scholar
  • 17 Hughes AJ, Daniel SE, Ben-Shlomo Y et al. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 2002; 125: 861-870
    CrossrefPubMedGoogle Scholar
  • 18 Aarsland D, Perry R, Larsen JP et al. Neuroleptic sensitivity in Parkinson’s disease and parkinsonian dementias. J Clin Psychiatry 2005; 66: 633-637
    PubMedGoogle Scholar
  • 19 McKeith I, O’Brien J, Walker Z et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007; 6: 305-313
    CrossrefPubMedGoogle Scholar
  • 20 Inui Y, Toyama H, Manabe Y et al. Evaluation of probable or possible dementia with lewy bodies using 123I-IMP brain perfusion SPECT, 123I-MIBG, and 99mTc-MIBI myocardial SPECT. J Nucl Med 2007; 48: 1641-1650
    CrossrefPubMedGoogle Scholar
  • 21 Berg D, Godau J, Walter U. Transcranial sonography in movement disorders. Lancet Neurol 2008; 7: 1044-1055
    CrossrefPubMedGoogle Scholar
  • 22 Spillantini MG, Schmidt ML, Lee VM et al. Alpha-synuclein in Lewy bodies. Nature 1997; 388: 839-840
    CrossrefPubMedGoogle Scholar
  • 23 Braak H, Rub U, Jansen Steur EN et al. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 2005; 64: 1404-1410
    CrossrefPubMedGoogle Scholar
  • 24 Parkkinen L, Pirttila T, Tervahauta M et al. Widespread and abundant alpha-synuclein pathology in a neurologically unimpaired subject. Neuropathology 2005; 25: 304-314
    CrossrefPubMedGoogle Scholar
  • 25 Parkkinen L, Kauppinen T, Pirttila T et al. Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia. Ann Neurol 2005; 57: 82-91
    CrossrefPubMedGoogle Scholar
  • 26 Kramer ML, Schulz-Schaeffer WJ. Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 2007; 27: 1405-1410
    CrossrefPubMedGoogle Scholar
  • 27 Andreasen N, Minthon L, Davidsson P et al. Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol 2001; 58: 373-379
    CrossrefPubMedGoogle Scholar
  • 28 Peskind ER, Riekse R, Quinn JF et al. Safety and acceptability of the research lumbar puncture. Alzheimer Dis Assoc Disord 2005; 19: 220-225
    CrossrefPubMedGoogle Scholar
  • 29 Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 2001; 310: 173-186
    CrossrefPubMedGoogle Scholar
  • 30 Reiber H. Liquorraeume, Liquorbildung und Liquorfluss. Stuttgart: Thieme Verlag; 2006
    Google Scholar
  • 31 May C, Kaye JA, Atack JR et al. Cerebrospinal fluid production is reduced in healthy aging. Neurology 1990; 40: 500-503
    CrossrefPubMedGoogle Scholar
  • 32 Zetterberg H, Ruetschi U, Portelius E et al. Clinical proteomics in neurodegenerative disorders. Acta Neurol Scand 2008; 118: 1-11
    PubMedGoogle Scholar
  • 33 Jellinger KA. Prevalence of Alzheimer lesions in Parkinson’s disease. Mov Disord 2003; 18: 1207-1208
    CrossrefPubMedGoogle Scholar
  • 34 Jellinger KA, Attems J. Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathol 2008; 115: 427-436
    CrossrefPubMedGoogle Scholar
  • 35 Mollenhauer B, Trenkwalder C, von Ahsen N et al. Beta-amlyoid 1-42 and tau-protein in cerebrospinal fluid of patients with Parkinson’s disease dementia. Dement Geriatr Cogn Disord 2006; 22: 200-208
    CrossrefPubMedGoogle Scholar
  • 36 Parnetti L, Tiraboschi P, Lanari A et al. Cerebrospinal fluid biomarkers in Parkinson’s disease with dementia and dementia with Lewy bodies. Biol Psychiatry 2008; 64: 850-855
    CrossrefPubMedGoogle Scholar
  • 37 Montine TJ, Shi M, Quinn JF et al. CSF Abeta(42) and tau in Parkinson’s disease with cognitive impairment. Mov Disord 2010; 25: 2682-2685
    CrossrefPubMedGoogle Scholar
  • 38 Compta Y, Marti MJ, Ibarretxe-Bilbao N et al. Cerebrospinal tau, phospho-tau, and beta-amyloid and neuropsychological functions in Parkinson’s disease. Mov Disord 2009; 24: 2203-2210
    CrossrefPubMedGoogle Scholar
  • 39 Siderowf A, Xie SX, Hurtig H et al. CSF amyloid {beta} 1-42 predicts cognitive decline in Parkinson disease. Neurology 2010; 75: 1055-1061
    CrossrefPubMedGoogle Scholar
  • 40 Alves G, Bronnick K, Aarsland D et al. CSF amyloid-beta and tau proteins, and cognitive performance, in early and untreated Parkinson’s disease: the Norwegian ParkWest study. J Neurol Neurosurg Psychiatry 2010; 81: 1080-1086
    CrossrefPubMedGoogle Scholar
  • 41 Gomperts SN, Rentz DM, Moran E et al. Imaging amyloid deposition in Lewy body diseases. Neurology 2008; 71: 903-910
    CrossrefPubMedGoogle Scholar
  • 42 Mollenhauer B, Cepek L, Bibl M et al. Tau protein, Abeta42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies. Dement Geriatr Cogn Disord 2005; 19: 164-170
    CrossrefPubMedGoogle Scholar
  • 43 Kasuga K, Tokutake T, Ishikawa A et al. Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 81: 608-610
    PubMedGoogle Scholar
  • 44 Bibl M, Mollenhauer B, Esselmann H et al. CSF amyloid-beta-peptides in Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia. Brain 2006; 129: 1177-1187
    CrossrefPubMedGoogle Scholar
  • 45 Bibl M, Esselmann H, Lewczuk P et al. Combined Analysis of CSF Tau, Abeta42, Abeta1-42% and Abeta1-40% in Alzheimer’s Disease, Dementia with Lewy Bodies and Parkinson’s Disease Dementia. Int J Alzheimers Dis 2010; Aug 24
    PubMedGoogle Scholar
  • 46 Mulugeta E, Londos E, Ballard C et al. CSF amyloid {beta}38 as a novel diagnostic marker for dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2011; 82: 160-164
    CrossrefPubMedGoogle Scholar
  • 47 Polymeropoulos MH, Lavedan C, Leroy E et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997; 276: 2045-2047
    CrossrefPubMedGoogle Scholar
  • 48 Mollenhauer B, Cullen V, Kahn I et al. Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 2008; 213: 315-325
    CrossrefPubMedGoogle Scholar
  • 49 Cookson MR. Pathways to Parkinsonism. Neuron 2003; 37: 7-10
    CrossrefPubMedGoogle Scholar
  • 50 Martin FL, Williamson SJ, Paleologou KE et al. Alpha-synuclein and the pathogenesis of Parkinson’s disease. Protein Pept Lett 2004; 11: 229-237
    CrossrefPubMedGoogle Scholar
  • 51 Tokuda T, Salem SA, Allsop D et al. Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease. Biochem Biophys Res Commun 2006; 349: 162-166
    CrossrefPubMedGoogle Scholar
  • 52 El-Agnaf OM, Salem SA, Paleologou KE et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 2006; 20: 419-425
    CrossrefPubMedGoogle Scholar
  • 53 Tokuda T, Qureshi MM, Ardah MT et al. Detection of elevated levels of {alpha}-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 2010; 20: 1766-1772
    PubMedGoogle Scholar
  • 54 Mollenhauer B, El-Agnaf OM, Marcus K et al. Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med 2010; 4: 683-699
    CrossrefPubMedGoogle Scholar
  • 55 Hong Z, Shi M, Chung KA et al. DJ-1 and {alpha}-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 2010; 13: 713-726
    PubMedGoogle Scholar
  • 56 Spies PE, Melis RJ, Sjogren MJ et al. Cerebrospinal fluid alpha-synuclein does not discriminate between dementia disorders. J Alzheimers Dis 2009; 16: 363-369
    PubMedGoogle Scholar
  • 57 Ohrfelt A, Grognet P, Andreasen N et al. Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders – a marker of synapse loss?. Neurosci Lett 2009; 450: 332-335
    CrossrefPubMedGoogle Scholar
  • 58 Noguchi-Shinohara M, Tokuda T, Yoshita M et al. CSF alpha-synuclein levels in dementia with Lewy bodies and Alzheimer’s disease. Brain Res 2009; 1251: 1-6
    CrossrefPubMedGoogle Scholar
  • 59 Mollenhauer B, Locascio JJ, Schulz-Schaeffer W et al. alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10: 230-240
    PubMedGoogle Scholar
  • 60 Schlossmacher MG, Mollenhauer B. Biomarker research in Parkinson’s disease: objective measures needed for patient stratification in future cause-directed trials. Biomark Med 2010; 4: 647-650
    CrossrefPubMedGoogle Scholar
  • 61 Bonifati V, Oostra BA, Heutink P. Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson’s disease. J Mol Med 2004; 82: 163-174
    CrossrefPubMedGoogle Scholar
  • 62 Waragai M, Wei J, Fujita M et al. Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s disease. Biochem Biophys Res Commun 2006; 345: 967-972
    CrossrefPubMedGoogle Scholar
  • 63 Choi J, Sullards MC, Olzmann JA et al. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem 2006; 281: 10816-10824
    CrossrefPubMedGoogle Scholar