Sympathetic noradrenergic before striatal dopaminergic denervation: Relevance to Braak staging of synucleinopathy

David S. Goldstein*, Courtney Holmes, La Toya Sewell, Mee Yeong Park, Yehonatan Sharabi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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-[ 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.

Original languageEnglish
Pages (from-to)57-61
Number of pages5
JournalClinical Autonomic Research
Volume22
Issue number1
DOIs
StatePublished - Feb 2012
Externally publishedYes

Funding

FundersFunder number
National Institutes of Health
National Institute of Neurological Disorders and StrokeZIANS003033

    Keywords

    • Braak
    • Norepinephrine
    • Parkinson
    • Sympathetic nervous system
    • Synuclein

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