title: Sympathetic noradrenergic before striatal dopaminergic denervation: relevance to Braak staging of synucleinopathy.
abstract: Braak's staging concept of Lewy body disease pathogenesis is based on a spatiotemporal sequence of alpha-synuclein deposition, with autonomic nervous system involvement before synucleinopathy in substantia nigra neurons. A patient with primary chronic autonomic failure underwent biennial brain 6-[(18)F]DOPA and myocardial 6-[(18)F]dopamine scanning over 4 years. Low myocardial radioactivity indicated cardiac noradrenergic denervation that persisted. Striatal 6-[(18)F]DOPA-derived radioactivity initially was normal, 2 years later was decreased subtly, and by 4 years was clearly decreased, accompanied by dementia and parkinsonism. In this case, neuroimaging evidence of cardiac noradrenergic denervation and subsequent progressive striatal dopaminergic denervation fit with Braak staging.
authors.affiliation: Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: Courtney
authors.initials: C
authors.lastname: Holmes
authors.forename: Latoya
authors.initials: L
authors.lastname: Sewell
authors.forename: Mee Yeong
authors.initials: MY
authors.lastname: Park
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
mesh_terms: D000368:Aged; D017763:Autonomic Denervation; D003704:Dementia / Q000150:complications / Q000503:physiopathology / Q000523:psychology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D018450:Disease Progression; D004298:Dopamine / Q000031:analogs & derivatives; D059290:Dopaminergic Neurons / Q000502:physiology*; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006212:Hallucinations / Q000209:etiology; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology*; D008297:Male; D017072:Neostriatum / Q000503:physiopathology*; D009638:Norepinephrine / Q000502:physiology*; D010300:Parkinson Disease / Q000150:complications / Q000503:physiopathology; D019275:Radiopharmaceuticals; D012791:Shy-Drager Syndrome / Q000503:physiopathology* / Q000523:psychology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D019275:Radiopharmaceuticals; D051844:alpha-Synuclein; C043437:fluorodopa F 18; C029253:6-fluorodopamine; D004295:Dihydroxyphenylalanine; D004298:Dopamine; D009638:Norepinephrine