The Syn-D Study: Detection of Cutaneous Phosphorylated Alpha-Synuclein and blood P-Tau 217 in Patients with Mild Cognitive Impairment
Christopher Gibbons1, Todd Levine2, Bailey Bellaire3, Roy Freeman4
1Beth Israel Deaconess Medical Center, 2Honor Health, 3CND Life Sciences, 4Beth Israel Deaconess Hosp
Objective:
To quantify the deposition of cutaneous phosphorylated a-synuclein (PSYN) and blood P-Tau 217 in patients with suspected dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage and track clinical and pathologic changes over time.
Background:
Dementia with Lewy bodies is a neurodegenerative disease characterized by progressive accumulation of a misfolded protein, phosphorylated a-synuclein (PSYN). Up to 30% of patients with Alzheimer’s disease may exhibit synuclein co-pathology in the central nervous system. An important unmet need exists for a validated, simple, reproducible marker of synuclein pathology in neurogenerative diseases at the prodromal stage.
Design/Methods:
After informed consent, detailed neurologic examinations, cognitive evaluation, orthostatic vital signs and questionnaires were completed. An independent expert panel of reviewers, blinded to pathology, reviewed de-identified medical records to confirm clinical diagnoses. Skin biopsies at the distal leg, distal thigh and posterior cervical sites were performed. Phosphorylated alpha-synuclein immunostaining was performed blinded to any clinical data. Serum biomarkers for AD pathology (P-Tau217) were measured.
Results:
To date, 98 subjects have been enrolled (44 with MCI-AD and 54 with MCI-DLB) from 15 study sites across the United States out of an anticipated 100 subjects. The mean age of the enrolled subjects is 73.5±6.4 years. Of the 98 enrolled subjects, 57/98 are P-SYN positive (58%). Complete unblinded baseline data will be presented at the AAN.
Conclusions:
Skin biopsies are a simple, low-risk outpatient procedure to test for phosphorylated alpha-synuclein as a diagnostic biomarker for the synucleinopathies. We will report the sensitivity of PSYN detection in patients with suspected MCI-DLB, and the rate of peripheral co-pathology with P-Tau217 in suspected MCI-AD cases. Although still blinded the data suggest that skin biopsy is an early, sensitive marker of synuclein detection prior to a clinical diagnosis of dementia.
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