Alpha-Synuclein Deposition Within Sympathetic Noradrenergic Neurons Is Associated With Myocardial Noradrenergic Deficiency in Neurogenic Orthostatic Hypotension

Hypertension
Risa IsonakaDavid S Goldstein

Abstract

Lewy body diseases involve neurogenic orthostatic hypotension (nOH), cardiac noradrenergic deficiency, and deposition of the protein AS (alpha-synuclein) in sympathetic ganglion tissue. Mechanisms linking these abnormalities are poorly understood. One link may be AS deposition within sympathetic neurons. We validated methodology to quantify AS colocalization with TH (tyrosine hydroxylase), a marker of sympathetic noradrenergic innervation, and assessed associations of AS/TH colocalization with myocardial norepinephrine content and cardiac sympathetic neuroimaging data in nOH. Postmortem sympathetic ganglionic AS/TH colocalization indices and myocardial norepinephrine contents were measured in 4 Lewy body and 3 rare non-Lewy body nOH patients. Sixteen Lewy body and 11 non-Lewy body nOH patients underwent in vivo skin biopsies and thoracic 18F-dopamine positron emission tomographic scanning, with cutaneous colocalization indices expressed versus cardiac 18F-dopamine-derived radioactivity. Ganglionic AS/TH colocalization indices were higher and myocardial norepinephrine lower in Lewy body than non-Lewy body nOH ( P=0.0020, P=0.014). The Lewy body nOH group had higher AS/TH colocalization indices in skin biopsies and lower myocardi...Continue Reading

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Citations

Dec 7, 2019·Journal of Neural Transmission·David S Goldstein
Nov 2, 2019·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Risa IsonakaDavid S Goldstein
Sep 19, 2020·Annals of Clinical and Translational Neurology·David S GoldsteinYehonatan Sharabi
Aug 28, 2020·Brain Sciences·Patrick S HosfordShahriar SheikhBahaei
Nov 21, 2020·Annals of Clinical and Translational Neurology·Guillaume LamotteDavid S Goldstein
Jun 3, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Risa IsonakaDerek P Narendra

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Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

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