Acta Neuropathologica

, Volume 114, Issue 5, pp 481–489 | Cite as

Neuronal and glial accumulation of α- and β-synucleins in human lipidoses

  • Kyoko Suzuki
  • Eizo Iseki
  • Takashi Togo
  • Akira Yamaguchi
  • Omi Katsuse
  • Kayoko Katsuyama
  • Seiichi Kanzaki
  • Kazumasa Shiozaki
  • Chiaki Kawanishi
  • Sumimasa Yamashita
  • Yukichi Tanaka
  • Shoji Yamanaka
  • Yoshio Hirayasu
Original Paper


A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both α- and β-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although α-synuclein has been implicated in several neurodegenerative disorders including Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear. In our present study, we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay–Sachs disease, metachromatic leukodystrophy, β-galactosialidosis and adrenoleukodystrophy, for the expression of α- and β-synucleins and the associated lipid storage levels. The accumulation of α-synuclein was found in brain tissue in not only cases of lysosomal storage diseases, but also in instances of adrenoleukodystrophy, which is a peroxisomal disease. α-synuclein was detected in both neurons and glial cells of patients with these two disorders, although its distribution was found to be disease-dependent. In addition, α-synuclein-positive neurons were also found to be NeuN-positive, whereas NeuN-negative neurons did not show any accumulation of this protein. By comparison, the accumulation of β-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of α- and β-synucleins in human lipidoses may be related to functional differences between these two proteins. In addition, the accumulation of α-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids.


α-synuclein Lysosome Peroxisome Lipid storage Neuronal nuclei 



We thank Dr. K. Ueda for his generous gift of antibodies, and we are grateful to Dr. Tatematsu and the late Dr. Yokoi for providing additional materials. The present study was supported in part by a Grant in Aid for Scientific Research (No.17790817) from the Japanese Society for the Promotion of Science.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Kyoko Suzuki
    • 1
  • Eizo Iseki
    • 2
  • Takashi Togo
    • 1
  • Akira Yamaguchi
    • 3
  • Omi Katsuse
    • 1
  • Kayoko Katsuyama
    • 3
  • Seiichi Kanzaki
    • 3
  • Kazumasa Shiozaki
    • 1
  • Chiaki Kawanishi
    • 1
  • Sumimasa Yamashita
    • 4
  • Yukichi Tanaka
    • 4
  • Shoji Yamanaka
    • 3
  • Yoshio Hirayasu
    • 1
  1. 1.Department of PsychiatryYokohama City University School of MedicineYokohamaJapan
  2. 2.Juntendo Tokyo Koto Geriatric Medical CenterJuntendo University School of MedicineTokyoJapan
  3. 3.Department of PathologyYokohama City University School of MedicineYokohamaJapan
  4. 4.Division of Neurology, PathologyKanagawa Children’s Medical CenterYokohamaJapan

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