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Zur postmortalen Diagnose des idiopathischen Morbus Parkinson

Postmortal diagnosis of Parkinson’s disease

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Zusammenfassung

Der idiopathische Morbus Parkinson ist eine stetig voranschreitende degenerative Erkrankung der zentralen, peripheren und enterischen Nervensysteme des Menschen. Neben der Substantia nigra erleiden eine Reihe weiterer Komponenten des motorischen Systems sowie zahlreiche Zentren des limbischen Systems und der autonomen Regulation schwere Zerstörungen. Nur wenige der zahlreichen Arten von Nervenzellen, die das menschliche Zentralnervensystem aufbauen, entwickeln die für den Morbus Parkinson charakteristischen und vornehmlich aus aggregiertem α-Synuklein bestehenden Lewy-Körper und Lewy-Neuriten, die zum vorzeitigen Absterben der betroffenen Neurone führen. Aufgrund der selektiven neuronalen Vulnerabilität ergibt sich eine charakteristische Verteilung der Veränderungen innerhalb des zentralen Nervensystems mit entsprechenden Einbußen der Funktionsfähigkeit zahlreicher Systeme. Die Veränderungen entstehen in zeitlich geordneter Reihenfolge. Der aszendierende pathologische Prozess ergreift innerhalb des Gehirns zunächst das dorsale Glossopharyngeus- und Vagusareal, zerstört nachfolgend weitgehend die Substantia nigra, erreicht dann den Mesokortex der Hirnrinde und dehnt sich von hier ausgehend in der Endphase der Erkrankung über weite Bereiche des Neokortex aus.

Abstract

Parkinson’s disease is a continuously progressive degenerative disorder of the central, peripheral and enteric human nervous systems. Not only the substantia nigra, but also a number of other components of the motor and limbic systems, as well as the autonomic regulation, suffer heavy damages. Only a few of the many types of nerve cells in the human central nervous system develop the characteristic Lewy bodies and Lewy neurites. They are composed primarily of aggregated α-synuclein and lead to the premature destruction of the affected neurons. Due to the selective neuronal vulnerability, a distinctive distribution of changes occurs within the central nervous system, leading to a corresponding loss of functionality in many systems. The changes occur in an ordered timely fashion. The ascending pathological process begins within the brain at the glossopharyngeal and vagal areas, nearly destroys the substantia nigra, and reaches the mesocortex of the gray matter. From here it expands to further areas of the neocortex, thereby marking the end phase of the disease.

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Literatur

  1. Bergeron C, Pollanen MS (1996) Pathogenesis of the Lewy body. In: Perry R, Mc Keith I, Perry E (eds) Dementia with Lewy bodies. Cambridge University Press, New York, pp 302–308

  2. Braak H, Braak E, Yilmazer D et al. (1994) Amygdala pathology in Parkinson’s disease. Acta Neuropathol 88:493–500

    Article  CAS  PubMed  Google Scholar 

  3. Braak H, Braak E, Yilmazer D et al. (1995) Nigral and extranigral pathology in Parkinson’s disease. J Neural Transm 46:15–31

    CAS  Google Scholar 

  4. Braak H, Braal E, Yilmazer D et al. (1995) Age-related changes of human cerebral cortex. In: Biomedical Health Research, Cruz-Sanchez FF, Ravid R, Cruzner ML (eds) Neuropathological diagnostic criteria for brain banking. IOS Press, Amsterdam, pp 14–19

  5. Braak H, De Vos RAI, Jansen ENH et al. (1998) Neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases. Prog Brain Res 117:267–285

    CAS  PubMed  Google Scholar 

  6. Braak E, Braak H (1999) Silver staining method for demonstrating Lewy bodies in Parkinson’s disease and argyrophilic oligodendrocytes in multiple system atrophy. J Neurosci Methods 87:111–115

    Article  CAS  PubMed  Google Scholar 

  7. Braak H, Sandmann-Keil D, Gai WP, Braak E (1999) Extensive axonal Lewy neurites in Parkinson’s disease: a novel pathological feature revealed by α-synuclein immunocytochemistry. Neurosci Lett 265:67–69

    Article  CAS  PubMed  Google Scholar 

  8. Braak H, Braak E (2000) Pathoanatomy of Parkinson’s disease. J Neurol 247:3–10

    Article  PubMed  Google Scholar 

  9. Braak H, Rüb U, Sandmann-Keil D et al. (2000) Parkinson’s disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system. Acta Neuropathol 99:489–495

    Article  CAS  PubMed  Google Scholar 

  10. Braak H, Del Tredici K, Bratzke H et al. (2002) Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). J Neurol 249 [Suppl]:111/I–111/V

  11. Braak H, Del Tredici K, Rüb U et al. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211

    Article  PubMed  Google Scholar 

  12. Clayton DF, George JM (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci 21:249–254

    Article  CAS  PubMed  Google Scholar 

  13. Del Tredici K, Rüb U, De Vos RAI et al. (2002) Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 61:413–426

    PubMed  Google Scholar 

  14. Dickson DW (1998) Aging in the central nervous system. In: Markesbery WR (ed) Neuropathology of dementing disorders. Arnold, London New York, pp 56–88

  15. Dickson DW (2000) Alzheimer-Parkinson disease overlap: neuropathology. In: Clark CM, Trojanowski JQ (eds) Neurodegenerative dementias. Clinical features and pathological mechanisms. McGraw-Hill, New York, pp 247–259

  16. Duda JE, Lee VMY, Trojanowski JQ (2000) Neuropathology of synuclein aggregates: new insights into mechanism of neurodegenerative diseases. J Neurosci Res 61:121–127

    Google Scholar 

  17. Fearnley JM, Lees AJ (1991) Aging and Parkinson’s disease: substantia nigra regional selectivity. Brain 114:2283–2301

    PubMed  Google Scholar 

  18. Fearnley JM, Lees AJ (1994) Pathology of Parkinson’s disease. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 545–554

  19. Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272

    CAS  PubMed  Google Scholar 

  20. Gai WP, Blessing WW, Blumbergs PC (1995) Ubiquitin-positive degenerating neurites in the brainstem in Parkinson’s disease. Brain 118:1447–1459

    PubMed  Google Scholar 

  21. Galvin JE, Lee VM, Trojanowski JQ (2001) Synucleinopathies: clinical and pathological implications. Arch Neurol 58:186–190

    Google Scholar 

  22. Gibb WRG (1991) Neuropathology of the substantia nigra. Eur Neurol 31:48–59

    PubMed  Google Scholar 

  23. Gibb WRG, Lees AJ (1991) Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson’s disease. J Neurol Neurosurg Psychiatry 54:388–396

    Google Scholar 

  24. Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2:492–501

    Article  CAS  PubMed  Google Scholar 

  25. Goedert M (2001) Parkinson’s disease and other alpha-synucleinopathies. Clin Chem Lab Med 39:308–312

    CAS  PubMed  Google Scholar 

  26. Halliday GM, Li YW, Blumbergs PC et al. (1990) Neuropathology of immunohistochemically identified brainstem neurons in Parkinson‘ s disease. Ann Neurol 27:373–385

    CAS  PubMed  Google Scholar 

  27. Hassler R (1938) Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J Psychol Neurol 48:387–476

    Google Scholar 

  28. Hellenbrand W, Vieregge P, Robra BP et al. (1993) Die Ätiologie des Morbus Parkinson. Eine epidemiologische Perspektive mit möglichen Implikationen für die Prävention. Nervenarzt 64:770–786

    CAS  PubMed  Google Scholar 

  29. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Google Scholar 

  30. Jellinger K (1987) The pathology of parkinsonism. In: Marsden CD, Fahn S (eds) Movement disorders 2. Butterworths, London, pp 124–165

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

    CAS  PubMed  Google Scholar 

  32. Koller WC (1992) How accurately can Parkinson’s disease be diagnosed? Neurology 42:6–16

    CAS  Google Scholar 

  33. Kretschmar HA, Neumann M (2000) Die neuropathologische Diagnostik neurodegenerativer und demenzieller Krankheiten. Pathologe 21:364–374

    Article  PubMed  Google Scholar 

  34. Krüger R, Müller T, Riess O (2000) Involvment of α-synuclein in Parkinson’s disease and other neurodegenerativ disorders. J Neural Transm 107:31–40

    Article  PubMed  Google Scholar 

  35. Lewy FH (1912) Paralysis agitans. I. Pathologische Anatomie. In: Lewandowski M (Hrsg) Handbuch der Neurologie. Springer, Berlin, S 920–933

  36. Lewy FH (1923) Die Lehre vom Tonus und der Bewegung, zugleich systematische Untersuchungen zur Klinik, Physiologie, Pathologie und Pathogenese der Paralysis agitans. Springer, Berlin

  37. Lowe J (1994) Lewy bodies. In: Calne DP (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 51–69

  38. Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8:2804–2815

    CAS  PubMed  Google Scholar 

  39. Murphy DD, Rueter SM, Trojanowski JQ, Lee VM (2000) Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J Neurosci 20:3214–3220

    CAS  PubMed  Google Scholar 

  40. Oertel H (1995) Parkinson’s disease: epidemiology, (differential) diagnosis, therapy, relation to dementia. Drug Res 45:386–389

    CAS  Google Scholar 

  41. Perry RH, Jaros EB, Irving D et al. (1996) What is the neuropathological basis of dementia associated with Lewy bodies? In: Perry RH, McKeith IG, Perry EK (eds) Dementia with Lewy bodies. Cambridge University Press, Cambridge New York, pp 212–223

  42. Poewe W, Oertel W (1992) Neue Entwicklungen in Diagnostik, Klinik und Therapie des Parkinson-Syndroms. In: Elger CE, Dengler R (Hrsg) Jahrbuch der Neurologie. Biermann, Zülpich, S 115–135

  43. Rüb U, Del Tredici K, Schultz C et al. (2002) Parkinson’s disease: the thalamic components of the limbic loop are severly impaired by α-synuclein immunopositive inclusion body pathology. Neurobiol Aging 23:245–254

    Article  PubMed  Google Scholar 

  44. Sandmann-Keil D, Braak H, Okochi M et al. (1999) Alpha-synuclein immunoreactive Lewy bodies and Lewy neurites in Parkinson’s disease are detectable by an advanced silver-staining technique. Acta Neuropathol 98:461–464

    Article  CAS  PubMed  Google Scholar 

  45. Schneider E (1997) Diagnostik und Therapie des Morbus Parkinson. De Gruyter, Berlin New York

  46. Scholz E, Oertel WH (1993) Parkinson-Syndrome. In: Brandt T, Dichgans J, Diener HC (Hrsg) Therapie und Verlauf neurologischer Erkrankungen. Kohlhammer, Stuttgart, S 927–968

  47. Schulz JB, Dichgans J (1999) Molecular pathogenesis of movement disorders: are protein aggregates a common link in neuronal degeneration. Curr Opin Neurol 12:433–439

    Article  CAS  PubMed  Google Scholar 

  48. Spillantini MG, Schmidt ML, Lee VMY et al. (1997) α-Synuclein in Lewy bodies. Nature 388:839–840

    Article  CAS  PubMed  Google Scholar 

  49. Spillantini MG, Goedert M (2000) The α-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Ann N Y Acad Sci 920:16–27

    CAS  PubMed  Google Scholar 

  50. Trojanowski JQ, Lee VMY (1998) Aggregation of neurofilament and α-synuclein proteins in Lewy bodies—implications for the pathogenesis of Parkinson disease and Lewy body dementia. Arch Neurol 55:151–152

    Article  CAS  PubMed  Google Scholar 

  51. Trojanowski JQ, Lee VMY (2000) „Fatal attractions“ of proteins. A comprehensive hypothetical mechanism underlying Alzheimer’s disease and other neurodegenerative disorders. Ann N Y Acad Sci 924:62–67

    CAS  PubMed  Google Scholar 

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Danksagung

Diese Arbeit entstand mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft und des Bundesministeriums für Forschung, Bildung und Technologie. Der besondere Dank der Autoren gebührt Frau I. Szasz für die Anfertigung der Graphiken.

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  1. Institut für Klinische Neuroanatomie, Johann Wolfgang Goethe Universität Frankfurt am Main

    D. Sandmann-Keil &  H. Braak

  2. Institut für Klinische Neuroanatomie, Johann Wolfgang Goethe Universität, Theodor-Stern-Kai 7, 60590, Frankfurt am Main

    H. Braak

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  1. D. Sandmann-Keil
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  2. H. Braak
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Correspondence to H. Braak.

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Sandmann-Keil, D., Braak, H. Zur postmortalen Diagnose des idiopathischen Morbus Parkinson. Pathologe 26, 214–220 (2005). https://doi.org/10.1007/s00292-004-0722-5

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