Sympathetic noradrenergic before striatal dopaminergic denervation: relevance to Braak staging of synucleinopathy
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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-[18F]DOPA and myocardial 6-[18F]dopamine scanning over 4 years. Low myocardial radioactivity indicated cardiac noradrenergic denervation that persisted. Striatal 6-[18F]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.
KeywordsParkinson Synuclein Braak Sympathetic nervous system Norepinephrine
This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. Ms. Tereza Jenkins (Clinical Neurocardiology Section) coordinated patient travel. Sandra Pechnik, RN (Clinical Neurocardiology Section) assisted with clinical procedures and scheduling.
Conflict of interest
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