Abstract Details

Title A Longitudinal Quantitative Assessment of Phosphorylated Alpha-Synuclein Deposition in Dementia with Lewy Bodies

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S1 - Innovations in Non-AD Dementia (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Background Dementia with Lewy bodies (DLB) is a neurodegenerative disease characterized by progressive accumulation of a misfolded protein, phosphorylated alpha-synuclein that can be quantified from standard punch biopsies.

Objective To report the quantitative change in cutaneous phosphorylated alpha-synuclein (P-SYN) in patients with dementia with Lewy bodies (DLB) over 6 months of longitudinal follow up in a blinded clinical trial.

Design/Methods After signed consent, study participants completed neurologic examinations (MDS-UPDRS III), medical history review and cognitive evaluation (MOCA). DLB was defined using consensus criteria for probable DLB. Skin biopsies (3mm) were taken from the distal leg, distal thigh and posterior cervical regions at baseline and 6 months with quantitation of P-SYN and intraepidermal nerve fiber density (INFD).

Results A total of 75 DLB participants had skin biopsies obtained at 2 time points (age 72.2±5.6 years: 10 Female, 65 Male). P-SYN was detected in 67/75 participants (89.3%). The total amount of P-SYN at baseline was 8.8±5.7 SU’s, and at 6 months the P-SYN amount increased to 11.1±5.6 SU’s (P<0.01). P-SYN burden increased in 42/67 patients, decreased in 14/67 patients and was stable in 11/67 patients. No adverse events related to biopsies were noted.

Conclusions Skin biopsies offer a simple, low-risk outpatient test to detect and quantify phosphorylated alpha-synuclein in patients with DLB. Quantitative measures of cutaneous deposition suggest an annual increase in P-SYN deposition of 52% in patients with DLB and suggest that skin biopsy can serve as a novel therapeutic target for pharmaceutical trials that seek to alter the natural history phosphorylated alpha-synuclein deposition or aggregation. The rapid increase in P-SYN in patients with DLB also suggests a leveraged population of patients appropriate for disease modifying therapies that could include clinical trials of shorter duration.

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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