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Updated: Mar 11, 2026
Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay
Published on: June 25, 2019
The Syn-sleep trial protocol: detection of cutaneous phosphorylated alpha-synuclein in REM sleep behavior disorder
Sarrah Marcotte1, Todd Levine1, Roy Freeman2
1CND Life Sciences, Scottsdale, AZ, USA.
Background:
Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal neurodegenerative disease of misfolded alpha-synuclein (P-SYN) with a high risk of phenoconversion to a clinically apparent synucleinopathy (including Parkinson's disease, multiple system atrophy, or dementia with Lewy bodies) over 15 years.
Objectives:
To determine rates of cutaneous P-SYN deposition in iRBD, to quantify changes in PSYN deposition over time, and to determine if P-SYN deposition patterns and amounts predict phenoconversion to a specific type of synucleinopathy.
Clinical Trial Protocol:
In a prospective, blinded study we will recruit 80 individuals with polysomnography confirmed iRBD or probable RBD using standard diagnostic criteria. Skin biopsies with dual immunohistochemical immunostaining for nerve fibers (protein gene product 9.5) and P-SYN will be completed at 3 sites using standard methodology. Quantitative measures of P-SYN and nerve fiber density will be measured blinded to any clinical data and will be followed longitudinally to determine the final clinical diagnosis.
Discussion:
Patients with iRBD are an important population to study due to the high rates of phenoconversion to clinically apparent synucleinopathy. Defining the frequency of P-SYN deposition and the risk of phenoconversion will aid in the development of future clinical trials that seek to alter the natural history of synucleinopathies.
