Objective: We present preliminary, cross-sectional data, on the in-vivo evaluation of pre-synaptic terminal density in the brain of patients with Multiple System Atrophy (MSA) compared with patients with Parkinson’s disease (PD) and healthy controls (HC), using the synaptic vesicle glycoprotein 2A (SV2A) selective PET radioligand [¹¹C]UCB-J.

Background: MSA is a progressive neurodegenerative disorder characterized by the prevalent accumulation of α-synuclein in oligodendroglial cells. α-synuclein exerts its physiological function in the synapses, thereby it is plausible that MSA may be characterized by extensive synaptic loss.

Method: Seven MSA patients (MSA-P=4; MSA-C=3) diagnosed according to the new 2022 Movement Disorders Society diagnostic criteria, underwent clinical evaluation, a 3T MRI, and an [¹¹C]UCB-J PET scan. Data were compared with 11 PD and 16 HC previously acquired as part of the MIND MAPS programme of studies. A region of interest (ROI) analysis was performed using the Clinical Imaging Centre atlas. The PET emission data and the arterial blood data collected at each scan were quantified using a one tissue-compartment model to derive the total volumes of distribution (V_T) for each ROI. DVR-1 was used as the outcome parameter for each PET scan, calculated using the centra semiovale as reference.

Results: Individuals with MSA showed decreased [¹¹C]UCB-J DVR-1, compared to HCs, in Putamen (-14.7%, p=0.004), Cerebellum (-31.3%, p=0.0001), and Brainstem (-53.6%, p=0.003) and, compared to PD, in the Cerebellum (-22.5%, p=0.02). MSA-P patients showed decreased [¹¹C]UCB-J DVR-1, compared with HCs, in the same regions and, compared with the PD and MSA-C groups, in the Putamen, (-14.6%, p=0.02, and -19.1%, p=0.036, respectively). A similar pattern of alterations in the MSA cohort was also observed using [¹¹C]UCB-J V_T and V_T/fp (VT corrected for the plasma free fraction) as alternative outcome parameters.

Conclusion: These findings provide preliminary evidence of a profound loss of synaptic density in the putamen, cerebellum, and brainstem, critical areas involved in the pathogenesis of MSA. The collection of clinical and imaging data for additional MSA patients at baseline as well as longitudinal follow-up to evaluate change over time is ongoing.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-in-vivo-study-of-regional-synaptic-density-loss-in-patients-with-multiple-system-atrophy-using-11cucb-j-pet-molecular-imaging/