Clinical, neuroimaging, and longitudinal progression characteristics of GBA1-associated Parkinson’s disease in a Northeast China cohort

GBA1 is a common genetic risk factor for Parkinson’s disease (PD), but PET/CT and longitudinal data in Chinese populations remain limited. We aimed to determine the frequency of GBA1-associated PD (GBA1-PD) in Northeast China and compare its clinical features, PET/CT images, and 3-year progression with non-GBA1-associated PD (NGBA1-PD). In this single-center observational cohort, 301 patients with PD underwent whole-exome sequencing, orthogonal validation and clinical assessment; 176 underwent 11C-CFT and 18F-FDG PET/CT, and 271 completed follow-up.

GBA1 variants were identified in 25 patients (8.31%). Compared with NGBA1-PD, GBA1-PD showed greater motor and cognitive impairment, higher PIGD proportion, worse sleep-related symptoms, lower striatal 11C-CFT uptake, and lower metabolism in the precuneus. Over 3 years, GBA1-PD showed trends toward faster motor and mood deterioration, although these differences did not remain significant after FDR correction.

These findings suggest distinct clinical and imaging features of GBA1-PD and potential value for prognostic stratification. Clinical trial number: Not applicable. We would like to thank Xiangyin Company and Professor Chaodong Wang from Chaoyang Hospital affiliated with Capital Medical University for their assistance with the validation of the GBA1 variants.

The work was supported by grants from the National Natural Science Foundation of China (No. 82571420) to YZ. Department of Neurology and Neuroscience Center, the First Hospital of Jilin University, Changchun, Jilin, China Xiaoxiao Du, Xinyu Wang, Pingping Shen, Yue Liang, Xiaoyue Lin, Jun Chen, Lin Pan & Ying Zhang The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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