Objective:

To define changes in cutaneous P-SYN quantification over 18 months in patients with Parkinson’s disease (PD) and idiopathic REM sleep behavior disorder (iRBD).

Background:

PD is characterized by progressive pathological alpha-synuclein (P-SYN) deposition in the central and peripheral nervous system. Skin biopsy has demonstrated high sensitivity and specificity for the detection of peripheral P-SYN in patients with PD. Recent technological advances now allow for quantitation of peripheral P-SYN, although longitudinal studies in PD have not been conducted.

Design/Methods:

After consent, participants with PD of Hoehn and Yahr stages 1, 2, 3 and iRBD completed neurological examinations, medical history, cognitive evaluation, motor assessments, olfactory testing (BSIT), orthostatic vitals, and neurodegenerative disease questionnaires.  Skin biopsies taken from the distal leg, distal thigh, and posterior cervical sites were performed on all participants with blinded quantitation of P-SYN. Participants will return for follow-up visits at 6-month intervals following the baseline visit.

Results:

At the time of abstract submission, 80 patients completed baseline testing (PD stage I: n=18, 63.3±6.1 years, 10 female; PD stage II: n=25, 67.7±8.7 years, 12 female; PD stage III: n=22, 72.8±9.7 years, 10 female; RBD: n=15, 65.7±9.4 years, 5 female).  Baseline P-SYN results were available in 72 patients and 63 (87.5%) were P-SYN positive. Analysis by disease severity revealed 10/11 (90.9%) iRBD patients were P-SYN positive, 15/18 (83.3%) in PD Stage I, 23/25 (92%) in PD Stage II, and 15/18 (83.3%) in Stage III patients were P-SYN positive. P-SYN quantitative assessment correlated with greater motor impairment, indicated by the UPDRS Pt. 3 (r=0.26, p=0.026).

Conclusions:

Cutaneous P-SYN was present in skin samples from patients with iRBD and in PD across Hoehn and Yahr stages 1-3. Preliminary data suggests a correlation between quantitative measures of P-SYN and disease severity. Longitudinal follow-up data collection is ongoing and will be reported at the 2026 AAN Meeting.