Skip to main content

Advertisement

SpringerLink
Log in

α-Synuclein pathology affecting Bergmann glia of the cerebellum in patients with α-synucleinopathies

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

Abstract

We carried out immunohistochemical examinations of the brains (cerebella) of patients who had suffered from Parkinson's disease (PD), diffuse Lewy body disease (DLBD) or multiple system atrophy (MSA), using antibodies specific for α-synuclein. α-Synuclein-positive doughnut-shaped structures were found occasionally in the cerebellar molecular layer in some of these patients. Double-labeling immunofluorescence and immunoelectron microscopy studies revealed that these α-synuclein-positive doughnut-shaped structures were located in the glial fibrillary acidic protein-positive radial processes of Bergmann glia, corresponding to the outer area of Lewy body-like inclusions, and consisted of granulo-filamentous structures. These findings indicate that, although not frequently, Bergmann glia of the cerebellum are also the targets of α-synuclein pathology in α-synucleinopathies such as PD, DLBD and MSA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

Similar content being viewed by others

References

  1. Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15:13–26

    CAS  PubMed  Google Scholar 

  2. Dickson DW (1999) Tau and synuclein and their role in neuropathology. Brain Pathol 9:657–661

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. Galvin JE, Lee VM-Y, Trojanowski JQ (2001) Synucleinopathies. Clinical and pathological implications. Arch Neurol 58:186–190

    PubMed  Google Scholar 

  5. Hashimoto M, Masliah E (1999) Alpha-synuclein in Lewy body disease and Alzheimer's disease. Brain Pathol 9:707–720

    PubMed  Google Scholar 

  6. Herndon RM, Rubinstein LJ, Freeman JM, Mathieson G (1970) Light and electron microscopic observations on Rosenthal fibers in Alexander's disease and in multiple sclerosis. J Neuropathol Exp Neurol 29:524–551

    CAS  PubMed  Google Scholar 

  7. Higuchi Y, Iwaki T, Tateishi J (1995) Neurodegeneration in the limbic and paralimbic system in progressive supranuclear palsy. Neuropathol Appl Neurobiol 21:246–254

    CAS  PubMed  Google Scholar 

  8. Hirano A (1971) Electron microscopy in neuropathology. In: Zimmermann HM (ed) Progress in neuropathology, vol. 1. Grune and Stratton, New York, pp 1–16

    Google Scholar 

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

    PubMed  Google Scholar 

  10. Itoh M, Watanabe Y, Watanabe M, Tanaka K, Wada K, Takashima S (1997) Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum. Brain Res 767:265–271

    Article  CAS  PubMed  Google Scholar 

  11. Iwaki T, Kume-Iwaki A, Liem RKH, Goldman JE (1989) αB-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. Cell 57:71–78

    CAS  PubMed  Google Scholar 

  12. Iwaki T, Kume-Iwaki A, Goldman JE (1990) Cellular distribution of αB-crystallin in non-lenticular tissues. J Histochem Cytochem 38:31–39

    PubMed  Google Scholar 

  13. Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345:27–32

    CAS  PubMed  Google Scholar 

  14. Kreutzberg GW, Blakemore WF, Graeber MB (1997) Cellular pathology of the central nervous system. In: Graham DI, Lantos PL (eds) Greenfield's neuropathology, vol 1, Arnold, London, pp 116–124

  15. McKeith IG, Galasko D, Kosaka K, et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124

    CAS  PubMed  Google Scholar 

  16. Murayama S, Arima K, Nakazato Y, Satoh J-I, Oda M, Inose T (1992) Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 2. Oligodendroglial cytoplasmic inclusions. Acta Neuropathol 84:32–38

    CAS  PubMed  Google Scholar 

  17. Piao Y-S, Wakabayashi K, Hayashi S, Yoshimoto M, Takahashi H (2000) Aggregation of α-synuclein/NACP in the neuronal and glial cells in diffuse Lewy body disease: a survey of six patients. Clin Neuropathol 19:163–169

    CAS  PubMed  Google Scholar 

  18. Piao Y-S, Hayashi S, Wakabayashi K, Kakita A, Aida I, Yamada M, Takahashi H (2002) Cerebellar cortical tau pathology in progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathol 103:469–474

    Article  CAS  PubMed  Google Scholar 

  19. Pridmore CL, Baraitser M, Harding B, Boyd SG, Kendall B, Brett EM (1993) Alexander's disease: clues to diagnosis. J Child Neurol 8:134–144

    CAS  PubMed  Google Scholar 

  20. Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M (1997) α-Synuclein in Lewy bodies. Nature 388:839–840

    CAS  PubMed  Google Scholar 

  21. 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

    PubMed  Google Scholar 

  22. Uéda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DAC, Kondo J, Ihara Y, Saitoh T (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci USA 90:11282–11286

    PubMed  Google Scholar 

  23. Wakabayashi K, Takahashi H (1996) Gallyas-positive, tau-negative glial inclusions in Parkinson's disease midbrain. Neurosci Lett 217:133–136

    Article  CAS  PubMed  Google Scholar 

  24. Wakabayashi K, Matsumoto K, Takayama K, Yoshimoto M, Takahashi H (1997) NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease. Neurosci Lett 239:45–48

    Article  CAS  Google Scholar 

  25. 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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Wakabayashi K, Hayashi S, Yoshimoto M, Kudo H, Takahashi H (2000) NACP/α-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson's disease brain. Acta Neuropathol 99:14–20

    PubMed  Google Scholar 

  28. Yoshimoto M, Iwai A, Kang D, Otero DAC, Xia Y, Saitoh T (1995) NACP, the precursor protein of the non-amyloid β/A4 protein (Aβ) component of Alzheimer disease amyloid, binds Aβ and stimulates Aβ aggregation. Proc Natl Acad Sci USA 92:9141–9145

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are indebted to Dr. T. Iwaki, Department of Neuropathology, Kyushu University, Fukuoka, Japan, and Dr. K. Tanaka, Department of Molecular Neuroscience, Tokyo Medical and Dental University, Tokyo, Japan, for anti-αB-crystallin antibody and anti-EAAT4 antibody, respectively. We also thank J. Takasaki, C. Tanda, S. Egawa, T. Hasegawa, Y. Ota and K. Honma for their technical assistance, and M. Machida, Ms. Abe and T. Koike for their secretarial assistance. This work was supported, in part, by a grant from the Research Committee on Neurodegenerative Diseases, the Ministry of Health, Labour and Welfare, Japan, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Author information

Authors and Affiliations

  1. Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, 951-8585, Niigata, Japan

    Yue-Shan Piao, Shintaro Hayashi, Akiyoshi Kakita & Hitoshi Takahashi

  2. The Brain Disease Research Center, Brain Research Institute, Niigata University, 1-757 Asahimachi, 951-8585, Niigata, Japan

    Akiyoshi Kakita

  3. Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 036-8562, Hirosaki, Japan

    Fumiaki Mori, Kunikazu Tanji & Koichi Wakabayashi

  4. Molecular Biology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical, 330-8530, Saitama, Japan

    Makoto Yoshimoto

Authors
  1. Yue-Shan Piao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumiaki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shintaro Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kunikazu Tanji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Makoto Yoshimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akiyoshi Kakita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koichi Wakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hitoshi Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yue-Shan Piao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Piao, YS., Mori, F., Hayashi, S. et al. α-Synuclein pathology affecting Bergmann glia of the cerebellum in patients with α-synucleinopathies. Acta Neuropathol 105, 403–409 (2003). https://doi.org/10.1007/s00401-002-0655-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-002-0655-0

Keywords

Search

Navigation