Objective: To investigate the distribution and potential influence of tau pathology in Parkinson’s disease (PD) patients with and without prodromal REM sleep behavior disorder (pRBD), using ¹⁸F-Florzolotau positron emission tomography (PET) imaging.To investigate the distribution and potential influence of tau pathology in Parkinson’s disease (PD) patients with and without prodromal REM sleep behavior disorder (pRBD), using ¹⁸F-Florzolotau positron emission tomography (PET) imaging.

Background: Recent models propose that PD can be stratified into the body-first and brain-first subtypes based on the origin of α-synuclein pathology. Importantly, this hypothesis suggests pRBD as a key marker to distinguish these two phenotypes(1). Meanwhile, several studies regarding PD pathogenesis have corroborated distinct patterns of tau accumulation. While tau co-pathology may play a critical role in α-synucleinopathy progression(2), whether tau pathology diverges across these putative PD subtypes has not been delineated.

Method: We recruited twenty-six PD patients and classified them into two groups based on the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ). Sixteen patients who scored ≤3 were classified as putative brain-first subtype (PDpRBD-), and ten patients who scored ≥6 as putative body-first subtype (PDpRBD+). All participants underwent clinical assessments and ¹⁸F-Florzolotau PET imaging. Intergroup differences and clinical correlations were assessed using voxel-based analyses.

Results: Voxel-based ¹⁸F-Florzolotau uptake was significantly higher in PDpRBD+ patients compared to the PDpRBD- group, particularly in the right precuneus and left posterior cingulate regions. Notably, in the putative body-first cohort, higher tau tracer binding in the right limbic system, specifically the right putamen (R=-0.831, P=0.003) and right insula (R=-0.790, P=0.007), was inversely correlated with cognitive performance, as measured by the Mini-Mental State Examination (MMSE) scores, after adjusting for age, gender, and education.

Conclusion: Our study demonstrated distinct patterns of tau tracer uptake between PDpRBD+ and PDpRBD- patients. Notably, the putative body-first phenotype exhibited a more extensive tau burden that correlated with cognitive impairment. These results provide in vivo imaging evidence on the tau pathology divergence of hypothesized PD subtypes.

Voxel-wise Tau PET comparison: PDpRBD+ vs PDpRBD-

Tau PET uptake and MMSE Correlation in PDpRBD+

References: 1. McKenna D, Peever J. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder. Mov Disord 2017;32(5):636–644. https://doi.org/10.1002/mds.27003
2. Vermilyea SC, Christensen A, Meints J, et al. Loss of tau expression attenuates neurodegeneration associated with α-synucleinopathy. Transl Neurodegener 2022;11(1):34. https://doi.org/10.1186/s40035-022-00309-x

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-18f-florzolotau-tau-pet-imaging-in-parkinsons-disease-with-and-without-probable-rem-sleep-behavior-disorder/