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Association of innervation-adjusted alpha-synuclein in arrector pili muscles with cardiac noradrenergic deficiency in autonomic synucleinopathies
- Source :
- Clinical Autonomic Research. 29:587-593
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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 0.8 or log AS/TH > 1.2 and had myocardial 18F-dopamine-derived radioactivity
- Subjects :
- Male
Pathology
medicine.medical_specialty
Synucleinopathies
Biopsy
Heart Ventricles
Shy-Drager Syndrome
030204 cardiovascular system & hematology
03 medical and health sciences
chemistry.chemical_compound
Sympathetic Fibers, Postganglionic
0302 clinical medicine
Atrophy
medicine
Humans
Aged
Skin
Alpha-synuclein
Lewy body
Tyrosine hydroxylase
Endocrine and Autonomic Systems
business.industry
Muscle, Smooth
Multiple System Atrophy
medicine.disease
Pathophysiology
chemistry
Positron-Emission Tomography
alpha-Synuclein
Synuclein
Female
Catecholaminergic cell groups
Neurology (clinical)
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 16191560 and 09599851
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Clinical Autonomic Research
- Accession number :
- edsair.doi.dedup.....e377ccffb586dfe21cb4c95316e87375