Skip to main content
Log in

α-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

We immunohistochemically examined the sympathetic ganglia (SG) and brains of 26 patients with multiple system atrophy (MSA), 19 age-matched controls, and 25 patients with amyotrophic lateral sclerosis (ALS). α-Synuclein-immunoreactive structures were found in the neuronal cytoplasm and processes of the SG in 11 of the 26 MSA cases (42.3%) and 1 of the 25 ALS cases (4%), but not in the 19 controls. No α-synuclein-immunoreactive structures were found in Schwann cells or the neuronal nucleus. Mean disease duration of MSA cases with α-synuclein-immunoreactive structures was significantly longer than that of MSA cases without α-synuclein-immunoreactive structures. α-Synuclein-immunoreactive structures in 4 cases proved to be Lewy bodies (LB) based on hematoxylin-eosin staining. A few LB were also found in the brains of 3 of these 4 cases. In the other 7 MSA cases, diffuse or focal neuronal cytoplasmic aggregates and swollen neurites were detected with α-synuclein immunostaining, but not with hematoxylin-eosin staining. However, a few LB-like structures with ring-like staining were observed in those aggregates, which suggested those aggregates had progressed to form LB. Immunoelectron microscopically, those aggregates were composed of filaments and granular materials which closely resembled the ultrastructural features of LB. We inferred that α-synuclein aggregates found in the SG in our study evidenced LB-related pathologies. MSA, a type of synucleinopathy, is characterized by glial cytoplasmic inclusions in oligodendrocytes, but also frequently develops LB pathology in the late stage, especially in the SG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1 A–C
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Arima K, Ueda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (1998) NACP/α-synuclein imunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in pontine nuclei in multiple system atrophy. Acta Neuropathol 96:439–444

    Article  CAS  PubMed  Google Scholar 

  2. Arima K, Ueda K, Sunohara N, Hirai S, Izumiyama Y, Tonozuka-Uehara H, Kawai M (1998) Immunoelectron-microscopic demonstration of NACP/α-synuclein-epitopes on the filamentous component of Lewy bodies in Parkinson’s disease and in dementia with Lewy bodies. Brain Res 808:93–100

    Article  CAS  PubMed  Google Scholar 

  3. Braak H, Del Tredici K, Rüb U, De Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 34:197–211

    Article  Google Scholar 

  4. Daniel S (1999) The neuropathology and neurochemistry of multiple system atrophy. In: Matias C, Bannister R (eds) Autonomic failure: a textbook of clinical disorders of the autonomic nervous system. Oxford University Press, Oxford, pp 321–328

  5. Del Tredici K, Rüb U, De Vos RA, Bohl JR, Braak H (2002) Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 61:413–426

    PubMed  Google Scholar 

  6. Dickson DW, Liu W-K, Hardy J, Farrer M, Mehta N, Uitti R, Mark M, Zimmerman T, Golbe L, Sage J, Sima, D’Amato C, Albin R, Gilman S, Yen S-H (1998) Widespread alterations of α-synuclein in multiple system atrophy. Am J Pathol 155:1241–1251

    Google Scholar 

  7. Dickson DW, Lin W, Liu W-K, Yen S-H (1999) Multiple system atrophy: a sporadic synucleinopathy. Brain Pathol 9:721–732

    CAS  PubMed  Google Scholar 

  8. Gai WP, Power JHT, Blumbergs PC, Blessing WW (1998) Multiple-system atrophy: a new α-synuclein disease? Lancet 352:547–548

    Article  CAS  PubMed  Google Scholar 

  9. Gai WP, Pountney DL, Power JHT, Li QX, Culvenor JG, McLean CA, Jensen PH, Blumbergs PC (2003) α-Synuclein fibrils constitute the central core of oligodendroglia inclusion filaments in multiple system atrophy. Exp Neurol 181:68–78

    Article  CAS  PubMed  Google Scholar 

  10. Galvin JE, Lee VM-Y, Trojanowski JQ (2001) Synucleinopathy: clinical and pathological implications. Arch Neurol 58:186–190

    Article  CAS  PubMed  Google Scholar 

  11. Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK (1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94–98

    Article  CAS  PubMed  Google Scholar 

  12. Graham JG, Oppenheimer DR (1969) Orthostatic hypertention and nicotine insensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 32:28–34

    CAS  PubMed  Google Scholar 

  13. Hayashida K, Oyanagi S, Mizutani Y, Yokochi M (1993) An early cytoplasmic change before Lewy body maturation: an ultrastructural study of the substantia nigra from an autopsy case of juvenile parkinsonism. Acta Neuropathol 85:445–448

    Article  CAS  PubMed  Google Scholar 

  14. Hishikawa N, Hashizume Y, Yoshida M, Sobue Gen (2001) Widespread occurrence of argyrophilic glial inclusions in Parkinson’s disease. Appl Neurobiol 27:362–372

    Article  CAS  Google Scholar 

  15. Hishikawa N, Hshizume Y, Yoshida M, Sobue Gen (2003) Clinical and neuropathological correlates of Lewy body disease. Acta Neuropathol 105:341–350

    Google Scholar 

  16. Iwanaga K, Wakabayashi K, Yoshimoto M, Tomita I, Satoh H, Takashima H, Satoh A, Seto M, Tsujihara M, Takahashi H (1999) Lewy body-type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body disease. Neurology 52:1269–1271

    CAS  PubMed  Google Scholar 

  17. Jellinger KA (2003) α-Synuclein pathology in Parkinson’s and Alzheimer’s desease brain: incidence and topographic distribution—a pilot study. Acta Neuropathol 106:191–201

    Article  PubMed  Google Scholar 

  18. Jellinger KA (2003) Neuropathological spectrum of synucleinopathy. Mov Disord 18 (Suppl 6):S2–S12

    Article  PubMed  Google Scholar 

  19. Kato S, Nakamura H (1990) Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol 79:584–594

    Article  CAS  PubMed  Google Scholar 

  20. Kawasaki H, Shimada H, Tomonaga M (1988) Morphological study on the Lewy bodies in the sympathetic ganglia of the aged persons (in Japanese). Nippon Ronen Igakkai Zasshi 25:282–291

    CAS  PubMed  Google Scholar 

  21. Lantos PL (1998) The definition of multiple system atrophy: a review of recent developments. J Neuropathol Exp Neurol 57:1099–1111

    CAS  PubMed  Google Scholar 

  22. Lowe J, Leigh N (2003) Disorders of movement and system degenerations. In: Graham D, Lantos PL (eds) Greenfield’s neuropathology, 7th edn, vol 2. Arnord, London, pp 343–346

  23. Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1999) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 57:690–698

    Google Scholar 

  24. Neuropathology groups of the Medical Research Council Cognitive Function and Aging Study (MRC CFAS) (2001) Pathological correlate of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 357:169–175

    Article  PubMed  Google Scholar 

  25. Nishie M, Mori F, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2004) Accumulation of phosphorylated α-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. Acta Neuropathol 107:292–298

    Article  CAS  PubMed  Google Scholar 

  26. Papp MI, Lantos PL (1992) Accumulation tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci 107:172–182

    Article  CAS  PubMed  Google Scholar 

  27. Papp MI, Lantos PL (1994) The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 117:235–243

    PubMed  Google Scholar 

  28. Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100

    Article  CAS  PubMed  Google Scholar 

  29. Parikh SM, Diedrich A, Biaggioni I, Robertson D (2002) The nature of autonomic dysfunction in multiple system atrophy. J Neurol Sci 200:1–10

    Article  PubMed  Google Scholar 

  30. Parkkinen L, Soininen H, Laakso M, Alafuzoff I (2001) α-Synuclein pathology is highly dependent on the case selection. Neuropathol Appl Neurobiol 27:314–325

    Article  CAS  PubMed  Google Scholar 

  31. Riku S, Hashizume Y (1984) A clinico-pathological study on multiple system atrophy, with special reference to its striato-nigral lesions and motor neuron involvements (in Japanese). Rinsyou Shinkei 24:552–561

    CAS  Google Scholar 

  32. Saito Y, Kawashima A, Ruberu NN, Fujiwara H, Koyama S, Sawabe M, Arai T, Nagura H, Yamanouti H, Hasegawa M, Iwatsubo T, Murayama S (2003) Accumulation of phosphorylated α-synuclein in aging human brain. J Neuropathol Exp Neurol 62:644–654

    CAS  PubMed  Google Scholar 

  33. Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998) Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 251:205–208

    Article  CAS  PubMed  Google Scholar 

  34. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 46:1470

    PubMed  Google Scholar 

  35. Tu P-H, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM-Y (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insolubleα-synuclein. Ann Neurol 44:415–422

    Article  CAS  PubMed  Google Scholar 

  36. Wakabayashi K (1989) Parkinson’s disease: the distribution of Lewy bodies in the peripheral autonomic nervous system (in Japanese). No To Shinkei 41:965–971

    CAS  PubMed  Google Scholar 

  37. Wakabayashi K, Takahashi H (1997) Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 38 (Suppl 2):2–7

    Google Scholar 

  38. Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182

    Article  CAS  PubMed  Google Scholar 

  39. Wakabayashi K, Hayashi S, Kakita A, Yamada M, Toyoshima Y, Yoshimoto M, Takahashi H (1998) Accumulation of NACP/α-synuclein is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol 96:445–452

    Article  CAS  PubMed  Google Scholar 

  40. Wenning GK, Ben-Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1995) Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry 58:160–166

    CAS  PubMed  Google Scholar 

  41. Wenning GK, Seppi K, Tison F, Jellinger K (2002) A novel grading scale for striatonigral degeneration (multiple system atrophy) J Neural Transm 109:307–320

    Google Scholar 

  42. Wenning GK, Colosimo C, Geser F, Poewe W (2004) Multiple system atrophy. Lancet Neurol 3:93–103

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported in part by grants from the Ministry of Health, Welfare and Labor of Japan.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mie Sone, Nozomi Hishikawa or Gen Sobue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sone, M., Yoshida, M., Hashizume, Y. et al. α-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy. Acta Neuropathol 110, 19–26 (2005). https://doi.org/10.1007/s00401-005-1013-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-005-1013-9

Keywords

Navigation