Objective: To study the cardiac sympathetic innervation and its relationship with the incidence of alpha-synuclein deposits in heart tissue of synucleinopathies and asymptomatic control patients.

Background: Early involvement of the peripheral autonomic system in neurologically unimpaired subjects could provide new biomarkers in neurodegenerative disease, particularly in PD. Cardiac uptake of MIBG (analog of norepinephrine) is decreased in the early stages of Parkinson’s disease (PD) probably as a consequence of an initial inclusion body formation in the sympathetic cardiac fibers.

Methods: We examined cardiac tissue from 125 autopsies, 37 subjects with synucleinopathy (PD, Lewy body dementia and incidental Lewy body disease) and 88 controls. Sections from the anterior left ventricle were immunohistochemically examined using antibodies against neurofilament (NF), tyrosine hydroxylase (TH) and phospho-alpha-synuclein (syn). Double immunofluorescence with NF-TH, TH-syn and TH-Ubicuitin, were also performed. Intensity of immunoreactivity (ir) in the nerve fibers was quantitatively analyzed using ImageJ software. Statistical analysis was carried out by means of Stata software.

Results: Phospho-synuclein deposits were observed in 90% of patients with synucleinopathy. NF-ir and TH-ir fibers were significantly decreased in the epicardium of synucleinopathies compared with control subjects (p<0.05). Among controls we found 10 incidental cases with syn aggregates in the sympathetic cardiac nerves. The density (TH-ir/μm2) of dopaminergic fibers was 25.65 in synucleinopathies, 35.21 in asymptomatic subjects with incidental cardiac aggregates and 42.19 in controls. The density of syn deposits in the peripheral nervous system was similar in all groups.

Conclusions: Cardiac Lewy body pathology was present in the majority of the patients with synucleinopathies. Synuclein deposits are also present in heart tissue of asymptomatic patients and it is associated with a loss of sympathetic nerve fibers. The loss of dopaminergic fibers in the peripheral nervous system increases as Lewy body aggregates follow a rostro – caudal gradient.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-aggregates-of-cardiac-sympathetic-nerves-in-synucleinopathies-and-in-neurologically-unimpaired-subjects-correlation-with-sympathetic-denervation/