Regular paper

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-HardyAffiliated withDepartment of Neurology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA e-mail: gwinn.katrina@mayo.edu, Tel.: +1-904-9537135, Fax: +1-904-9537117
  • , N. D. MehtaAffiliated withDepartment of Pharmacology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
  • , M. FarrerAffiliated withDepartment of Pharmacology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
  • , D. MaraganoreAffiliated withDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA
  • , M. MuenterAffiliated withDepartment of Neurology Mayo Clinic Scottsdale, Scottsdale, Arizona, USA
  • , S. -H. YenAffiliated withDepartment of Pharmacology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
  • , J. HardyAffiliated withDepartment of Pharmacology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
  • , D. W. DicksonAffiliated withDepartment of Pathology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA

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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 Dementia Lewy body Neuropathology Synuclein Western blotting