The Syn-D study: detection of cutaneous phosphorylated alpha-synuclein in mild cognitive impairment a trial protocol

Abstract

Background: Skin biopsies have >95% sensitivity and specificity to detect the presence of phosphorylated alpha-synuclein (P-SYN). Objective: To determine the frequency of cutaneous P-SYN in patients with mild cognitive impairment (MCI) due to suspected Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Design, Setting and Participants: The Syn-D study is a multicenter prospective clinical trial from ~10 centers across the United States that includes patients with MCI-AD or MCI-DLB. Methods: Patients will undergo skin biopsies for detection of P-SYN and plasma biomarkers for ptau-217 to determine biomarker positivity rates at the MCI stage and will be followed longitudinally to determine final clinical diagnosis as defined by an expert panel of clinicians blinded to biomarker results. Main Outcomes and Measures: The co-primary outcomes include: 1) The sensitivity of skin biopsy detection of P-SYN in patients with clinical diagnoses of MCI due to DLB or AD at baseline and at 12-month follow-up 2) To report the frequency with which cutaneous deposition of P-SYN and blood-based AD biomarkers co-exist in a population of patients with MCI. Discussion: This will be the first in-vivo study to determine the co-existence of biomarkers for both diseases as a surrogate for co-pathology. Trial registration: NCT05479552.