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

Katrina Gwinn-Hardy, Nitin D. Mehta, Matt Farrer, Demetrius Maraganore, Manfred Muenter, Shu Hui Yen, John Hardy, Dennis W. Dickson

Research output: Contribution to journalArticle

141 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)663-672
Number of pages10
JournalActa neuropathologica
Volume99
Issue number6
DOIs
StatePublished - Jun 2000

Keywords

  • Dementia
  • Lewy body
  • Neuropathology
  • Synuclein
  • Western blotting

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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