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Acta Neuropathologica

, Volume 110, Issue 3, pp 298–305 | Cite as

Abundant neuritic inclusions and microvacuolar changes in a case of diffuse Lewy body disease with the A53T mutation in the α-synuclein gene

  • Keiji Yamaguchi
  • Elizabeth J. Cochran
  • Jill R. Murrell
  • Mihael H. Polymeropoulos
  • Kathleen M. Shannon
  • R. Anthony Crowther
  • Michel Goedert
  • Bernardino GhettiEmail author
Case Report

Abstract

We report here a case of diffuse Lewy body disease with the A53T mutation in the α-synuclein gene. The proband presented at the age of 41 years with parkinsonism that was poorly responsive to levodopa. She subsequently developed cognitive impairment and moderate dementia, and died at the age of 50. Her father, paternal grandfather and uncle were all reported to have suffered from Parkinson’s disease. Staining of tissue sections from the proband’s brain with hematoxylin-eosin and α-synuclein antibodies showed small numbers of Lewy bodies in a few brain regions. This contrasted with large numbers of Lewy neurites and neuroaxonal spheroids in many brain regions. By electron microscopy, Lewy neurites consisted of abnormal filaments and dense granular material. Isolated filaments resembled those previously described in idiopathic Parkinson’s disease and dementia with Lewy bodies. They were decorated by antibodies specific for the N and C termini of α-synuclein, indicating the presence of the full-length protein. Nucleus accumbens and the lower layers in limbic areas of the cerebral cortex showed prominent vacuolation, with frequent clustering of microvacuoles around Lewy neurites. Nerve cell loss was most extensive in dorsal motor nucleus of the vagus nerve, substantia nigra and nucleus basalis of Meynert. Neurofibrillary tangles and senile plaques were not observed. However, in several brain regions, a few widely scattered tau-positive nerve cell bodies and neurites were present. By electron microscopy, Alzheimer-type paired helical and straight filaments were seen.

Keywords

Diffuse Lewy body disease A53T mutation α-Synuclein Lewy neurites Microvacuolar changes 

Notes

Acknowledgements

We gratefully acknowledge C. Alyea, R. Richardson and B. Dupree for technical help, and B. Glazier and U. Küderli for photographic assistance. We thank P. Davies, M. Hasegawa and T. Iwatsubo for their kind gift of antibodies. This study was supported in part by PHS P30 AG10133.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Keiji Yamaguchi
    • 1
  • Elizabeth J. Cochran
    • 2
  • Jill R. Murrell
    • 1
  • Mihael H. Polymeropoulos
    • 3
  • Kathleen M. Shannon
    • 2
  • R. Anthony Crowther
    • 4
  • Michel Goedert
    • 4
  • Bernardino Ghetti
    • 1
    Email author
  1. 1.Department of Pathology and Laboratory Medicine, Division of NeuropathologyIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Neurological Sciences and PathologyRush University Medical CenterChicagoUSA
  3. 3.Novartis PharmaceuticalsGaithersburgUSA
  4. 4.Medical Research Council Laboratory of Molecular BiologyCambridgeUK

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