Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p.
The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-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 alpha-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight alpha-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with alpha-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.
Gwinn-Hardy
K
K
Department of Neurology, Mayo Clinic Jacksonville, FL 32224, USA. gwinn.katrina@mayo.edu
Mehta
N D
ND
Farrer
M
M
Maraganore
D
D
Muenter
M
M
Yen
S H
SH
Hardy
J
J
Dickson
D W
DW
D001921:Brain / Q000473:pathology; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein