Parkinson's disease: a broken nosology.
Parkinson's disease (PD) is a clinical diagnosis. We argue here that if we are to make progress in understanding its underlying pathogenesis, there is a need to have a pathological definition of disease that includes the presence of Lewy bodies and nigral loss in the ventrolateral tier of the pars compacta of the substantia nigra. Using such a definition, there is only one certain and known cause: mutations in the alpha-synuclein gene. However, the phenotype of this one known cause is broader than PD and encompasses Lewy body dementia.
Hardy
John
J
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. hardyj@mail.nih.gov
Lees
Andrew J
AJ
D000067699:Ataxin-3; D000067528:Ataxins; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012097:Repressor Proteins; D013378:Substantia Nigra / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C092341:ATXN3 protein, human; D000067699:Ataxin-3