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.
Similar content being viewed by others
References
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
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
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
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
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
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
Dickson DW, Lin W, Liu W-K, Yen S-H (1999) Multiple system atrophy: a sporadic synucleinopathy. Brain Pathol 9:721–732
Gai WP, Power JHT, Blumbergs PC, Blessing WW (1998) Multiple-system atrophy: a new α-synuclein disease? Lancet 352:547–548
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
Galvin JE, Lee VM-Y, Trojanowski JQ (2001) Synucleinopathy: clinical and pathological implications. Arch Neurol 58:186–190
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
Graham JG, Oppenheimer DR (1969) Orthostatic hypertention and nicotine insensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 32:28–34
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
Hishikawa N, Hashizume Y, Yoshida M, Sobue Gen (2001) Widespread occurrence of argyrophilic glial inclusions in Parkinson’s disease. Appl Neurobiol 27:362–372
Hishikawa N, Hshizume Y, Yoshida M, Sobue Gen (2003) Clinical and neuropathological correlates of Lewy body disease. Acta Neuropathol 105:341–350
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
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
Jellinger KA (2003) Neuropathological spectrum of synucleinopathy. Mov Disord 18 (Suppl 6):S2–S12
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
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
Lantos PL (1998) The definition of multiple system atrophy: a review of recent developments. J Neuropathol Exp Neurol 57:1099–1111
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
Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1999) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 57:690–698
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
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
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
Papp MI, Lantos PL (1994) The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 117:235–243
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
Parikh SM, Diedrich A, Biaggioni I, Robertson D (2002) The nature of autonomic dysfunction in multiple system atrophy. J Neurol Sci 200:1–10
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
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
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
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
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
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
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
Wakabayashi K, Takahashi H (1997) Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 38 (Suppl 2):2–7
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
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
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
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
Wenning GK, Colosimo C, Geser F, Poewe W (2004) Multiple system atrophy. Lancet Neurol 3:93–103
Acknowledgement
This work was supported in part by grants from the Ministry of Health, Welfare and Labor of Japan.
Author information
Authors and Affiliations
Corresponding authors
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00401-005-1013-9