Advertisement

Cytoskeletal pathology of the Lewy bodies

  • K. Jellinger
  • C. Bancher
  • H. Lassmann
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

Lewy bodies (LB), a major anatomical hallmark of Parkinson’s disease (PD), represent abnormal intracytoplasmic neuronal inclusions that show typical antigenic profiles for both the classical and cortical type. Classical or subcortical LB show a strong reaction of the periphery with monoclonal antibodies (mABs) to phosphorylated epitopes of neurofilament proteins (NFP), to micro tubule-associated proteins MAP 2 and MAP 1 (only on cryostate sections), to a mAB to paired helical filaments (PHF) which recognizes ubiquitin, and to polyclonal ABs to ubiquitin, while the core strongly reacts with a mAB to PHF (3.39) that also recognizes determinants of ubiquitin. Cortical LB show diffuse reaction with ABs to NFP and PHF, although no PHF or 15 nm filaments are found in these inclusions. Ultra-structurally, most of the filaments in LB appear to be related to NFP, part of which are uncovered by phosphatase pretreatment indicating that abnormal phosphorylation of NFP plays a role in their pathogenesis. The frequent coexistence of both LB and neurofibrillary tangles (NFT) in the same brain and even in the same neuronal perikaryon, and the sharing of several epitopes have suggested some common pathogenic relations. While both LB and NFT have been shown to contain ubiquitin, a polypeptide required for the ATP-dependent non-lysosomal protein breakdown, LB do not react with tau-protein, the major component of PHF. These data indiciate that ubiquinated proteins in LB and NFT are different: phosphorylated NFP appear to be the major component of LB, while abnormal phosphorylation of tau is suggested to be the first step in the process of NFT formation, and ubiquination may reflect a fruitless attempt of proteolytic degradation. Biochemical changes of cytoskeletal elements may be reflected by the ultrastructural changes in these neuronal inclusions, and reflect the molecular correlate of the different appearance of classical and cortical types of LB, the pathogenesis of which remains to be elucidated.

Keywords

Lewy Body Cytoskeletal Element Locus Ceruleus Paired Helical Filament Melanin Granule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bancher C, Lassmann H, Budka H, Jellinger K, Grundke-Igbal I, Iqbal K, Wiche G, Seitelberger F, Wisniewski HM (1988) Antigenic profiles of Lewy bodies: Immunocytochemical evidence for protein phosphorylation and ubiquination. J Neuropath Exp Neurol 47 (in press)Google Scholar
  2. Dickson DW, Davies P, Mayeux R, Crystal H, Horoupian DS, Thompson A, Goldman JE (1987) Diffuse Lewy body disease: Neuropathological and biochemical studies of six patients. Acta Neuropathol (Berlin) 75: 8–15Google Scholar
  3. Forno LS (1986) The Lewy body in Parkinson’s disease. Adv Neurol 45: 35–43Google Scholar
  4. Forno LS, Langston JW, DeLanney LE, Irwin I, Ricaurte GA (1986) Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 20: 449–455PubMedCrossRefGoogle Scholar
  5. Forno LS, Langston JW, DeLanney LE, Irwin I (1988) An electron microscopic study of MPTP-induced inclusion bodies in an old monkey. Brain Res 448: 150–157PubMedCrossRefGoogle Scholar
  6. Gibb WRG (1986) Idiopathic Parkinson’s disease and the Lewy body disorders. Neuropathol Appl Neurobiol 12: 223–234PubMedCrossRefGoogle Scholar
  7. Grundke-Iqbal I, Igbal K, Tung Y-C, Quinlain M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83: 4913–4917PubMedCrossRefGoogle Scholar
  8. Jellinger K (1987) The pathology of parkinsonism. In Marsden CD, Fahn St (eds) Movement disorders II. Butterworths, London, pp 124–162Google Scholar
  9. Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y (1988) Lewy bodies are ubiquinated. Acta Neuropathol (Berlin) 75: 345–353CrossRefGoogle Scholar
  10. Nakashima S, Ikuta F (1984) Tyrosine hydroxylase proteins in Lewy bodies of parkinsonism and senile brain. J Neurol Sci 66: 91–96PubMedCrossRefGoogle Scholar
  11. Pappola MA (1986) Lewy bodies of Parkinson’s disease: Immunoelectron microscopic demonstration of neurofilament antigens in constituent filaments. Arch Pathol Lab Med 110: 1160–1163Google Scholar
  12. Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquination is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci USA 84: 3033–3036PubMedCrossRefGoogle Scholar
  13. Yen SH, Dickson DW, Peterson C, Goldman JE (1986) Cytoskeletal abnormalities in neuropathology. Prog Neuropathol 6: 63–90Google Scholar

Copyright information

© Springer-Verlag/Wien 1989

Authors and Affiliations

  • K. Jellinger
    • 1
  • C. Bancher
    • 2
  • H. Lassmann
    • 2
  1. 1.Ludwig Boltzmann-Institute of Clinical NeurobiologyLainz HospitalViennaAustria
  2. 2.Neurological InstituteUniversity of Vienna, School of MedicineViennaAustria

Personalised recommendations