Background: We recently reported that α-synuclein can be detected within cutaneous
autonomic nerve fibers of patients with Parkinson’s disease (PD) (Wang N. et. al.
Neurology 2013). The long-term implication of this finding on autonomic nerve fiber
structure and function is unknown. Objective: To determine the relationship between
α-synuclein deposition, autonomic nerve fiber density and autonomic function in a
longitudinal study of patients with PD. Methods: Twenty-eight individuals with PD
and 23 age and gender-matched healthy control subjects had clinical examinations,
autonomic function testing and skin biopsies from 4 sites taken at an initial visit
and repeated 1 year later. Skin biopsies were stained for PGP9.5, and total α-synuclein (both phosphorylated
and non-phosphorylated). The ratio of α-synuclein to nerve innervation (α-synuclein
ratio) was calculated for each sample. The density of intra-epidermal (IENFD), sudomotor
(SGNFD) and pilomotor (PMNFD) nerve fibers was determined. The initial α-synuclein
ratio was compared against the change in nerve fiber density (IENFD, SGNFD and PMNFD)
over 1 year. Results: Patients with PD had higher α-synuclein ratios compared to controls
within pilomotor nerves and sudomotor nerves at all sites (P < 0.01, all biopsy sites). Higher α-synuclein ratios measured at the baseline visit
were correlated with a greater decline in SNGFD (r = −0.46, P < 0.01) and PMNFD (r = −0.61, P < 0.001) 1 year later. There was a correlation between higher α-synuclein ratios and greater
decline in heart rate variability (r = 0.39, P < 0.05), Valsalva Ratio (r = 0.42, P < 0.05) and orthostatic hypotension (r = 0.46, P < 0.01). Discussion: These data support the pathophysiologic association between α-synuclein
deposition, autonomic nerve fiber degeneration and autonomic dysfunction in individuals
with PD. The results of this longitudinal study further support the role of the α-synuclein
as a biomarker in patients with Parkinson disease. Acknowledgement: Study supported
by the RJG Foundation (CHG), and the Michael J. Fox Foundation (RF).
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© 2015 Published by Elsevier Inc.