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Absence of α-synuclein pathology in postencephalitic parkinsonism

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Abstract

Postencephalitic parkinsonism (PEP), a chronic complication of encephalitis lethargica, is a tauopathy characterized by multisystem neuronal loss and gliosis with widespread neurofibrillary lesions composed of both 3- and 4-repeat (3R and 4R) tau isoforms. Previous immunohistochemical studies in a small number of PEP cases demonstrated absence of Lewy bodies as well as the lack of other α-synuclein pathology, classifying PEP as a “pure” tauopathy. Neuropathologic examination of 10 brains with clinico-pathologically verified PEP confirmed widespread neurodegeneration in subcortical and brainstem areas associated with multifocal neurofibrillary pathology comprising both 3R and 4R tau. Very rare β-amyloid deposits were observed in two elderly patients, while Lewy bodies and neurites or any other α-synuclein deposits were completely absent. The causes and molecular background of total absence of α-synuclein pathology in PEP, in contrast to most other tauopathies, remain as unknown as the pathogenesis of PEP.

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References

  1. Arai T, Ikeda K, Akiyama H, Nonaka T, Hasegawa M, Ishiguro K, Iritani S, Tsuchiya K, Iseki E, Yagishita S, Oda T, Mochizuki A (2004) Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration. Ann Neurol 55:72–79

    Article  PubMed  CAS  Google Scholar 

  2. Buee-Scherrer V, Buee L, Leveugle B, Perl DP, Vermersch P, Hof PR, Delacourte A (1997) Pathological tau proteins in postencephalitic parkinsonism: comparison with Alzheimer’s disease and other neurodegenerative disorders. Ann Neurol 42:356–359

    Article  PubMed  CAS  Google Scholar 

  3. Calne DB, Stern GM, Laurence DR, Sharkey J, Armitage P (1969) l-dopa in postencephalitic parkinsonism. Lancet 1:744–746

    Article  PubMed  CAS  Google Scholar 

  4. Caparros-Lefebvre D, Cabaret M, Godefroy O, Steinling M, Remy P, Samson Y, Petit H (1998) PET study and neuropsychological assessment of a long-lasting post-encephalitic parkinsonism. J Neural Transm 105:489–495

    Article  PubMed  CAS  Google Scholar 

  5. Delacourte A, Buee L (2000) Tau pathology: a marker of neurodegenerative disorders. Curr Opin Neurol 13:371–376

    Article  PubMed  CAS  Google Scholar 

  6. Delacourte A (2005) Alzheimer’s disease: a true tauopathy fueled by amyloid precursor protein dysfunction. In: Fisher A (ed) Progress in Alzheimer’s and Parkinson’s. Taylor & Francis, London, pp 301–307

    Google Scholar 

  7. DelleDonne A, Klos KJ, Fujishiro H, Ahmed Z, Parisi JE, Josephs KA, Frigerio R, Burnett M, Wszolek ZK, Uitti RJ, Ahlskog JE, Dickson DW (2008) Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol 65:1074–1080

    Article  PubMed  Google Scholar 

  8. Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, Jellinger K, Lantos PL, Lippa CF, Mirra SS, Tabaton M, Vonsattel JP, Wakabayashi K, Litvan I (2002) Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61:935–946

    PubMed  CAS  Google Scholar 

  9. Dickson DW, Fujishiro H, Delledonne A, Menke J, Ahmed Z, Klos KJ, Josephs KA, Frigerio R, Burnett M, Parisi JE, Ahlskog JE (2008) Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease. Acta Neuropathol 115:437–444

    Article  PubMed  Google Scholar 

  10. Duvoisin RC, Lobo-Antunes J, Yahr MD (1972) Response of patients with postencephalitic Parkinsonism to levodopa. J Neurol Neurosurg Psychiatry 35:487–495

    Article  PubMed  CAS  Google Scholar 

  11. Espinoza M, de Silva R, Dickson DW, Davies P (2008) Differential incorporation of tau isoforms in Alzheimer’s disease. J Alzheimers Dis 14:1–16

    PubMed  CAS  Google Scholar 

  12. Feany MB, Mattiace LA, Dickson DW (1996) Neuropathologic overlap of progressive supranuclear palsy, Pick’s disease and corticobasal degeneration. J Neuropathol Exp Neurol 55:53–67

    Article  PubMed  CAS  Google Scholar 

  13. Fenelon G, Goetz CG, Karenberg A (2006) Hallucinations in Parkinson disease in the prelevodopa era. Neurology 66:93–98

    Article  PubMed  Google Scholar 

  14. Foley PB (2009) Encephalitis lethargica and influenza. I. The role of the influenza virus in the influenza pandemic of 1918/1919. J Neural Transm 116:143–150

    Article  PubMed  Google Scholar 

  15. Forman MS, Schmidt ML, Kasturi S, Perl DP, Lee VM, Trojanowski JQ (2002) Tau and alpha-synuclein pathology in amygdala of Parkinsonism-dementia complex patients of Guam. Am J Pathol 160:1725–1731

    PubMed  CAS  Google Scholar 

  16. Geddes JF, Hughes AJ, Lees AJ, Daniel SE (1993) Pathological overlap in cases of parkinsonism associated with neurofibrillary tangles. A study of recent cases of postencephalitic parkinsonism and comparison with progressive supranuclear palsy and Guamanian parkinsonism-dementia complex. Brain 116(Pt 1):281–302

    Article  PubMed  Google Scholar 

  17. Geser F, Winton MJ, Kwong LK, Xu Y, Xie SX, Igaz LM, Garruto RM, Perl DP, Galasko D, Lee VM, Trojanowski JQ (2008) Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Acta Neuropathol 115:133–145

    Article  PubMed  CAS  Google Scholar 

  18. Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640

    Article  PubMed  CAS  Google Scholar 

  19. Hallervorden J (1935) Anatomische Untersuchungen zur Pathogenese des postencephalitischen Parkinsonismus. Dtsch Z Nervenheilk 136:68–77

    Article  Google Scholar 

  20. Haraguchi T, Ishizu H, Terada S, Takehisa Y, Tanabe Y, Nishinaka T, Kawai K, Kuroda S, Komoto Y, Namba M (2000) An autopsy case of postencephalitic parkinsonism of von Economo type: some new observations concerning neurofibrillary tangles and astrocytic tangles. Neuropathology 20:143–148

    Article  PubMed  CAS  Google Scholar 

  21. Henry JM, Jellinger KA (2003) Postencephalitic parkinsonism. In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 143–149

    Google Scholar 

  22. Hernandez F, Avila J (2007) Tauopathies. Cell Mol Life Sci 64:2219–2233

    Article  PubMed  CAS  Google Scholar 

  23. Hof PR, Charpiot A, Delacourte A, Buee L, Purohit D, Perl DP, Bouras C (1992) Distribution of neurofibrillary tangles and senile plaques in the cerebral cortex in postencephalitic parkinsonism. Neurosci Lett 139:10–14

    Article  PubMed  CAS  Google Scholar 

  24. Hunter KR, Stern GM, Sharkey J (1970) Levodopa in postencephalitic parkinsonism. Lancet 2:1366–1367

    Article  PubMed  CAS  Google Scholar 

  25. Jellinger KA (1999) Movement disorders with tau protein cytoskeletal pathology. Adv Neurol 80:303–311

    PubMed  CAS  Google Scholar 

  26. Jellinger KA (2004) Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm 111:1219–1235

    Article  PubMed  CAS  Google Scholar 

  27. Jellinger KA (2005) The pathology of Parkinson’s disease—recent advances. In: Gálvez-Jiménez N (ed) Scientific basis for the treatment of Parkinson’s disease, 2nd edn. Taylor & Francis, London, pp 53–85

    Google Scholar 

  28. Jellinger KA (2007) More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains. Acta Neuropathol 114:299–303

    Article  PubMed  Google Scholar 

  29. Jellinger KA (2007) Lewy body disorders. In: Youdim MBH, Riederer P, Mandel SA, Battistin L, Lajtha A (eds) Degenerative diseases of the nervous system. Springer Science, New York, pp 267–343

    Google Scholar 

  30. Jellinger KA, Attems J (2007) Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 113:107–117

    Article  PubMed  CAS  Google Scholar 

  31. Jellinger KA (2008) A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol 116:1–16

    Article  PubMed  CAS  Google Scholar 

  32. Jellinger KA (2009) Lewy body/alpha-synucleinopathy in schizophrenia and depression: a preliminary neuropathological study. Acta Neuropathol 117:423–427

    Article  PubMed  CAS  Google Scholar 

  33. Josephs KA, Parisi JE, Dickson DW (2002) Alpha-synuclein studies are negative in postencephalic parkinsonism of von Economo. Neurology 59:645–646

    PubMed  Google Scholar 

  34. Katsuse O, Iseki E, Arai T, Akiyama H, Togo T, Uchikado H, Kato M, de Silva R, Lees A, Kosaka K (2003) 4-repeat tauopathy sharing pathological and biochemical features of corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol 106:251–260

    Article  PubMed  Google Scholar 

  35. Keith-Rokosh J, Ang LC (2008) Progressive supranuclear palsy: a review of co-existing neurodegeneration. Can J Neurol Sci 35:602–608

    PubMed  CAS  Google Scholar 

  36. Lee VM, Giasson BI, Trojanowski JQ (2004) More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases. Trends Neurosci 27:129–134

    Article  PubMed  CAS  Google Scholar 

  37. Lees AJ (2003) Parkinson’s syndrome associated with neurofibrillary degeneration and tau pathologic findings. Mov Disord 18(Suppl 6):S28–S33

    Article  PubMed  Google Scholar 

  38. Litvan II, Jankovic J, Goetz CG, Wenning GK, Sastry N, Jellinger K, McKee A, Lai EC, Brandel JP, Verny M, Ray-Chaudhuri K, Pearce RK, Bartko JJ, Agid Y (1998) Accuracy of the clinical diagnosis of postencephalitic parkinsonism: a clinicopathologic study. Eur J Neurol 5:451–457

    Article  PubMed  Google Scholar 

  39. Mandal PK, Pettegrew JW, Masliah E, Hamilton RL, Mandal R (2006) Interaction between Abeta peptide and alpha synuclein: molecular mechanisms in overlapping pathology of Alzheimer’s and Parkinson’s in dementia with Lewy body disease. Neurochem Res 31:1153–1162

    Article  PubMed  CAS  Google Scholar 

  40. McCall S, Vilensky JA, Gilman S, Taubenberger JK (2008) The relationship between encephalitis lethargica and influenza: a critical analysis. J Neurovirol 14:177–185

    Article  PubMed  CAS  Google Scholar 

  41. Miklossy J, Steele JC, Yu S, McCall S, Sandberg G, McGeer EG, McGeer PL (2008) Enduring involvement of tau, beta-amyloid, alpha-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC). Acta Neuropathol 116:625–637

    Article  PubMed  CAS  Google Scholar 

  42. Mori H, Nishimura M, Namba Y, Oda M (1994) Corticobasal degeneration: a disease with widespread appearance of abnormal tau and neurofibrillary tangles, and its relation to progressive supranuclear palsy. Acta Neuropathol 88:113–121

    Article  PubMed  CAS  Google Scholar 

  43. Mortimer PP (2009) Was encephalitis lethargica a post-influenzal or some other phenomenon? Time to re-examine the problem. Epidemiol Infect 137:449–455

    Article  PubMed  CAS  Google Scholar 

  44. Oyanagi K, Tsuchiya K, Yamazaki M, Ikeda K (2001) Substantia nigra in progressive supranuclear palsy, corticobasal degeneration, and parkinsonism-dementia complex of Guam: specific pathological features. J Neuropathol Exp Neurol 60:393–402

    PubMed  CAS  Google Scholar 

  45. Parkkinen L, Pirttila T, Alafuzoff I (2008) Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance. Acta Neuropathol 115:399–407

    Article  PubMed  Google Scholar 

  46. Picard F, Hirsch E, Salmon E, Marescaux C, Collard M (1996) Parkinsonian syndrome and post-encephalitic stereotyped involuntary movements responsive to l-dopa. Rev Neurol (Paris) 152:267–271

    CAS  Google Scholar 

  47. Ravenholt RT, Foege WH (1982) 1918 influenza, encephalitis lethargica, parkinsonism. Lancet 2:860–864

    Article  PubMed  CAS  Google Scholar 

  48. Shao CY, Crary JF, Rao C, Sacktor TC, Mirra SS (2006) Atypical protein kinase C in neurodegenerative disease II: PKCiota/lambda in tauopathies and alpha-synucleinopathies. J Neuropathol Exp Neurol 65:327–335

    Article  PubMed  CAS  Google Scholar 

  49. Soto C, Estrada LD (2008) Protein misfolding and neurodegeneration. Arch Neurol 65:184–189

    Article  PubMed  Google Scholar 

  50. Tabaton M, Perry G, Autilio-Gambetti L, Manetto V, Gambetti P (1988) Influence of neuronal location on antigenic properties of neurofibrillary tangles. Ann Neurol 23:604–610

    Article  PubMed  CAS  Google Scholar 

  51. Togo T, Dickson DW (2002) Ballooned neurons in progressive supranuclear palsy are usually due to concurrent argyrophilic grain disease. Acta Neuropathol (Berl) 104:53–56

    Article  Google Scholar 

  52. Tolnay M, Probst A (1999) REVIEW: tau protein pathology in Alzheimer’s disease and related disorders. Neuropathol Appl Neurobiol 25:171–187

    Article  PubMed  CAS  Google Scholar 

  53. Torvik A, Meen D (1966) Distribution of the brain stem lesions in postencephalitic Parkinsonism. Acta Neurol Scand 42:415–425

    Article  PubMed  CAS  Google Scholar 

  54. Tsuboi Y, Ahlskog JE, Apaydin H, Parisi JE, Dickson DW (2001) Lewy bodies are not increased in progressive supranuclear palsy compared with normal controls. Neurology 57:1675–1678

    PubMed  CAS  Google Scholar 

  55. Uchikado H, DelleDonne A, Uitti R, Dickson DW (2006) Coexistence of PSP and MSA: a case report and review of the literature. Acta Neuropathol 111:186–192

    Article  PubMed  Google Scholar 

  56. Uchikado H, Lin WL, DeLucia MW, Dickson DW (2006) Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65:685–697

    Article  PubMed  CAS  Google Scholar 

  57. Ward CD (2003) Neuropsychiatric interpretations of postencephalitic movement disorders. Mov Disord 18:623–630

    Article  PubMed  Google Scholar 

  58. Wenning GK, Jellinger K, Litvan I (1997) Supranuclear gaze palsy and eyelid apraxia in postencephalitic parkinsonism. J Neural Transm 104:845–865

    Article  PubMed  CAS  Google Scholar 

  59. Yamazaki M, Hasegawa M, Mori O, Murayama S, Tsuchiya K, Ikeda K, Chen KM, Katayama Y, Oyanagi K (2005) Tau-positive fine granules in the cerebral white matter: a novel finding among the tauopathies exclusive to parkinsonism-dementia complex of Guam. J Neuropathol Exp Neurol 64:839–846

    Article  PubMed  Google Scholar 

  60. Zaccai J, Brayne C, McKeith I, Matthews F, Ince PG (2008) Patterns and stages of alpha-synucleinopathy: relevance in a population-based cohort. Neurology 70:1042–1048

    Article  PubMed  CAS  Google Scholar 

  61. Zhukareva V, Shah K, Uryu K, Braak H, Del Tredici K, Sundarraj S, Clark C, Trojanowski JQ, Lee VM (2002) Biochemical analysis of tau proteins in argyrophilic grain disease, Alzheimer’s disease, and Pick’s disease: a comparative study. Am J Pathol 161:1135–1141

    PubMed  CAS  Google Scholar 

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Acknowledgments

The author thanks Mrs. V. Rappelsberger for excellent laboratory work and Mr. E. Mitter-Ferstl, PhD, for secretarial and computer work. The study was supported by the Society for Support of Research in Experimental Neurology, Vienna, Austria.

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  1. Institute of Clinical Neurobiology, Kenyongasse 18, 1070, Vienna, Austria

    Kurt A. Jellinger

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Jellinger, K.A. Absence of α-synuclein pathology in postencephalitic parkinsonism. Acta Neuropathol 118, 371–379 (2009). https://doi.org/10.1007/s00401-009-0537-9

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