Abstract Details

Title A Novel Diagnostic Method for Detection and Quantitation of Cutaneous Phosphorylated Alpha-synuclein

Topic Movement Disorders

Presentation(s) S26 - Movement Disorders: Basic Science (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Background Synucleinopathies include Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). Early and accurate diagnosis of synucleinopathies remain a challenge although recent advances using skin immunofluorescent immunostaining of P-SYN from skin biopsies have offered a major diagnostic breakthrough. There is an ongoing need for an objective, continuous, quantitative measure of P-SYN deposition to monitor disease progression and the response to disease modifying interventions.

Objective To develop a novel, continuous, quantitative method for analysis of cutaneous phosphorylated alpha-synuclein (P-SYN).

Design/Methods We created a novel artificial intelligence (AI) driven protein detection algorithm to quantify misfolded proteins within cutaneous axons. We studied 20 patients each with PD, MSA, DLB, PAF and healthy controls. All subjects had 3mm skin biopsies at the distal leg, distal thigh and posterior cervical region with immunostaining for P-SYN and with protein gene product 9.5. All tissue sections underwent complete confocal digitization and AI driven quantitation of nerve fibers and intra-axonal P-SYN.

Results : We created an AI driven heatmap of P-SYN overlaying each tissue section to define the location and quantity of P-SYN within nerve fiber subtypes. 300 biopsies from 100 participants were reviewed. Diagnostic concordance between pathologic review of glass slides and AI augmented reading was 99.3% with P-SYN detected in 80/80 synucleinopathies and 0/20 healthy controls. AI assisted pathologic reading was >99% reproducible and augmented differentiation between synucleinopathy subtypes.

Conclusions We have initiated a program for whole slide digitization combined with artificial intelligence assisted detection of pathologic proteins. The application output provides heatmap assisted visualization of pathology with quantitative analysis of abnormal proteins by tissue region that improve detection of P-SYN with continuous, quantitative outputs. Digital pathology with artificial intelligence assisted pathologic quantitation may make a substantial contribution to the neurodegenerative disease field and bring novel diagnostic advances into mainstream medical care.

Authors/Disclosures
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center) PRESENTER	Dr. Gibbons has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Autonomic Neuroscience. 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.
Bailey Bellaire (CND Life Sciences)	No disclosure on file
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 $10,000-$49,999 for serving on a Speakers Bureau for Grifols. 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.
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.