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

139 Citations (Scopus)

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
StatePublished - Jun 2000

Fingerprint

Synucleins
Dementia
Chromosomes
Antibodies
Lewy Bodies
Parkinson Disease
Lewy Body Disease
Brain
Neuroglia
Psychotic Disorders
Genes
Neuropathology
Molecular Weight
Mutation

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkonsonism and dementia linked to chromosome 4p. / Gwinn-Hardy, Katrina; Mehta, Nitin D.; Farrer, Matt; Maraganore, Demetrius; Muenter, Manfred; Yen, Shu Hui; Hardy, John; Dickson, Dennis W.

In: Acta Neuropathologica, Vol. 99, No. 6, 06.2000, p. 663-672.

Research output: Contribution to journalArticle

Gwinn-Hardy, K, Mehta, ND, Farrer, M, Maraganore, D, Muenter, M, Yen, SH, Hardy, J & Dickson, DW 2000, 'Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkonsonism and dementia linked to chromosome 4p', Acta Neuropathologica, vol. 99, no. 6, pp. 663-672.
Gwinn-Hardy K, Mehta ND, Farrer M, Maraganore D, Muenter M, Yen SH et al. Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkonsonism and dementia linked to chromosome 4p. Acta Neuropathologica. 2000 Jun;99(6):663-672.
Gwinn-Hardy, Katrina ; Mehta, Nitin D. ; Farrer, Matt ; Maraganore, Demetrius ; Muenter, Manfred ; Yen, Shu Hui ; Hardy, John ; Dickson, Dennis W. / Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkonsonism and dementia linked to chromosome 4p. In: Acta Neuropathologica. 2000 ; Vol. 99, No. 6. pp. 663-672.
@article{c213c0c9c24e408a89b62e3383f08854,
title = "Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkonsonism and dementia linked to chromosome 4p",
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.",
keywords = "Dementia, Lewy body, Neuropathology, Synuclein, Western blotting",
author = "Katrina Gwinn-Hardy and Mehta, {Nitin D.} and Matt Farrer and Demetrius Maraganore and Manfred Muenter and Yen, {Shu Hui} and John Hardy and Dickson, {Dennis W}",
year = "2000",
month = "6",
language = "English (US)",
volume = "99",
pages = "663--672",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkonsonism and dementia linked to chromosome 4p

AU - Gwinn-Hardy, Katrina

AU - Mehta, Nitin D.

AU - Farrer, Matt

AU - Maraganore, Demetrius

AU - Muenter, Manfred

AU - Yen, Shu Hui

AU - Hardy, John

AU - Dickson, Dennis W

PY - 2000/6

Y1 - 2000/6

N2 - 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.

AB - 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.

KW - Dementia

KW - Lewy body

KW - Neuropathology

KW - Synuclein

KW - Western blotting

UR - http://www.scopus.com/inward/record.url?scp=0034069848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034069848&partnerID=8YFLogxK

M3 - Article

C2 - 10867800

AN - SCOPUS:0034069848

VL - 99

SP - 663

EP - 672

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 6

ER -