Acta Neuropathologica

, Volume 99, Issue 6, pp 663–672

Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p

  • K. Gwinn-Hardy
  • N. D. Mehta
  • M. Farrer
  • D. Maraganore
  • M. Muenter
  • S. -H. Yen
  • J. Hardy
  • D. W. Dickson
Regular paper

DOI: 10.1007/s004010051177

Cite this article as:
Gwinn-Hardy, K., Mehta, N., Farrer, M. et al. Acta Neuropathol (2000) 99: 663. doi:10.1007/s004010051177

Abstract

The identification of the α-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of α-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson’s disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the α-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight α-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with α-synuclein immunostaining, including pleomorphic Lewy bodies, synuclein-positive glial inclusions and widespread, severe neuritic dystrophy. We also discuss the relationship of this familial disorder to a Lewy body disease clinical spectrum, ranging from Parkinson’s disease to dementia with psychosis.

Key words DementiaLewy bodyNeuropathologySynucleinWestern blotting

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • K. Gwinn-Hardy
    • 1
  • N. D. Mehta
    • 2
  • M. Farrer
    • 2
  • D. Maraganore
    • 3
  • M. Muenter
    • 4
  • S. -H. Yen
    • 2
  • J. Hardy
    • 2
  • D. W. Dickson
    • 5
  1. 1.Department of Neurology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA e-mail: gwinn.katrina@mayo.edu, Tel.: +1-904-9537135, Fax: +1-904-9537117US
  2. 2.Department of Pharmacology, Mayo Clinic Jacksonville, Jacksonville, Florida, USAUS
  3. 3.Department of Neurology, Mayo Clinic, Rochester, Minnesota, USAUS
  4. 4.Department of Neurology Mayo Clinic Scottsdale, Scottsdale, Arizona, USAUS
  5. 5.Department of Pathology, Mayo Clinic Jacksonville, Jacksonville, Florida, USAUS