Abstract Details

Title The Syn-D Study: Detection of Cutaneous Phosphorylated Alpha-Synuclein and blood P-Tau 217 in Patients with Mild Cognitive Impairment

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S1 - Innovations in Non-AD Dementia (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

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.

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.

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.

Authors/Disclosures
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center) PRESENTER	Dr. Gibbons has received personal compensation for serving as an employee of CND Life Sciences. Dr. Gibbons has stock in CND Life Sciences. Dr. Gibbons has received publishing royalties from a publication relating to health care. Dr. Gibbons has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Advisor with Department of Justice.
Todd D. Levine, MD (Honor Health)	Dr. Levine has received personal compensation for serving as an employee of CND life sciences . Dr. Levine has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Nufactor. Dr. Levine has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for PNA. Dr. Levine has stock in CND Life Sciences. Dr. Levine has stock in Corinthian reference lab.
Bailey Bellaire (CND Life Sciences)	Bailey Bellaire has received personal compensation for serving as an employee of CND Life Sciences.
Roy L. Freeman, MD (Beth Israel Deaconess Hosp)	Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regenacy. Dr. Freeman has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurobo. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli-Lilly. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Freeman has stock in Neurobo. Dr. Freeman has stock in Cutaneous NeuroDiagnostics. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck.

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