Nov 2, 2019

Association of innervation-adjusted alpha-synuclein in arrector pili muscles with cardiac noradrenergic deficiency in autonomic synucleinopathies

Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society
Risa IsonakaD S Goldstein

Abstract

Autonomic synucleinopathies feature deposition of the protein alpha-synuclein (AS) in neurons [e.g., Lewy body neurogenic orthostatic hypotension (nOH)] or glial cells (multiple system atrophy, MSA). AS in skin biopsies might provide biomarkers of these diseases; however, this approach would be complicated or invalidated if there were substantial loss of AS-containing nerves. We report AS content in arrector pili muscles in skin biopsies after adjustment for local innervation in patients with Lewy body nOH or MSA. Cardiac sympathetic neuroimaging by myocardial 18F-dopamine positron emission tomography (PET) was done to examine pathophysiological correlates of innervation-adjusted AS. Thirty-one patients (19 Lewy body nOH, 12 MSA) underwent thoracic 18F-dopamine PET and skin biopsies. AS signal intensity analyzed by immunofluorescence microscopy was adjusted for innervation by the ratio of AS to protein gene product (PGP) 9.5, a pan-axonal marker (Harvard lab site), or the ratio of AS to tyrosine hydroxylase (TH), an indicator of catecholaminergic neurons (NIH lab site). The Lewy body nOH group had higher ratios of AS/PGP 9.5 or log AS/TH than did the MSA group (0.89 ± 0.05 vs. 0.66 ± 0.04, -0.13 ± 0.05 vs. -1.60 ± 0.33; p < 0.0...Continue Reading

  • References45
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References

  • References45
  • Citations1

Citations

Mentioned in this Paper

Biological Markers
Myocardial Disorder
Positron-Emission Tomography
Neurons
Biopsy of Skin Procedure
SNCA
Myocardium
Immunofluorescence Microscopy
Neuroglia
Nerve Supply

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