Objective: To compare the presence of symptoms suggestive of synucleinopathy between PSP-parkinsonism (PSP-P), Parkinson’s disease (PD) and PSP-Richardson syndrome (PSP-RS).

Background: Clinical signs with high predictive positive value for Lewy-type synucleinopathy to date have mostly been compared between PSP-RS, PD and healthy controls (HC), but not PSP-P.

Method: In this cross-sectional study of the Barcelona PSP Registry, we included 74 subjects (16 PSP-P, 20 PSP-RS and 20 PD fulfilling “probable” or “clinically established” of their respective diagnostic criteria, and 20 HC) without significant cognitive impairment (Montreal Cognitive Assessment > 17 points). REM sleep behaviour disorder (RBD) was evaluated through an interview conducted by a neurologist specialized in sleep disorders. Hyposmia was assessed with the University of Pennsylvania Smell Identification Test and orthostatic hypotension with an orthostatic test. CSF alpha-synuclein (asyn) seed amplification assay (SAA) was performed in 3 HC, 11 PD, 13 PSP-P and 16 PSP-RS. Statistical analyses included non-parametric group comparisons and logistic regression analyses. p < 0.05 was considered significant.

Results: The median age was 69 years [95% CI: 66–74], and 42% of participants were women, with no differences between groups. RBD was more frequent in PD (65%, p<0.001), PSP-P (50%, p=0.005), and PSP-RS (35%, p=0.044) compared to HC (5%). RBD tended to precede the onset of parkinsonism in PD (54%) but occurred afterwards in PSP-P and PSP-RS (88% and 86%, respectively; OR: 7.6 [1.2–48.0], p=0.031). Hyposmia was frequent in PD (88%), PSP-P (69%), and PSP-RS (60%), all significantly different from HC (15%). An abnormal orthostatic test was more frequent in PD (40%) than HC (0%, p=0.003) and PSP-P (0%, p=0.005). These symptoms were not associated with worse motor or cognitive status in PSP. Regarding CSF asyn-SAA results, all PD cases were positive, while all HC cases were negative. Among PSP, 10% had positive results, all still considered probable PSP-P despite the result. No differences in hyposmia, RBD, or orthostatism were found between PSP with positive and negative CSF asyn-SAA.

Conclusion: Symptoms suggestive of alpha-synucleinopathy are common in PSP despite negative asyn-SAA results. This supports the idea that pathology topography is more relevant than the underlying protein aggregate type. [Funded by Fundació La Marató de TV3]

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-features-suggestive-of-alpha-synucleinopathy-in-progressive-supranuclear-palsy/