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  • Review Article
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Linking the cerebellum to Parkinson disease: an update

Nature Reviews Neurology volume 19, pages 645–654 (2023)Cite this article

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Abstract

Parkinson disease (PD) is characterized by heterogeneous motor and non-motor symptoms, resulting from neurodegeneration involving various parts of the central nervous system. Although PD pathology predominantly involves the nigral–striatal system, growing evidence suggests that pathological changes extend beyond the basal ganglia into other parts of the brain, including the cerebellum. In addition to a primary involvement in motor control, the cerebellum is now known to also have an important role in cognitive, sleep and affective processes. Over the past decade, an accumulating body of research has provided clinical, pathological, neurophysiological, structural and functional neuroimaging findings that clearly establish a link between the cerebellum and PD. This Review presents an overview and update on the involvement of the cerebellum in the clinical features and pathogenesis of PD, which could provide a novel framework for a better understanding the heterogeneity of the disease.

Key points

  • Emerging evidence underscores the involvement of the cerebellum in the pathophysiology and pathogenesis of Parkinson disease (PD).

  • Anatomical investigations have revealed robust connectivity between the cerebellum and basal ganglia, encompassing dopaminergic projections that link the two regions.

  • Research spanning the past two decades has elucidated the presence of neurodegeneration and α-synuclein pathology in the cerebellum of people with PD.

  • Functional and connectivity analyses have highlighted distinct alterations in specific cerebellar areas that correlate with different clinical symptoms of PD.

  • Advances in physiological studies of the cerebellar circuitry in PD promise novel insights and provide a comprehensive framework for comprehending the heterogeneity of the disease.

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Fig. 1: Parkinson disease-related cerebellar circuitry.
Fig. 2: Distribution of cerebellar pathology in Parkinson disease.

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Acknowledgements

This Review was not funded. W.L. received grant support from National Natural Science Foundation of China (NSFC 32220103006, 82271524). T.L. received grant support from the National Natural Science Foundation of China (NSFC 82001483).

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Authors and Affiliations

  1. Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, China

    Tianbai Li & Weidong Le

  2. Institute of Neurology, Sichuan Academy of Medical Sciences, Sichuan Provincial Hospital, Chengdu, China

    Weidong Le

  3. Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA

    Joseph Jankovic

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  1. Tianbai Li
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  3. Joseph Jankovic
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T.L. contributed to review of the literature and the original draft. W.L. and J.J. contributed to review of the literature, editing and critique.

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Correspondence to Weidong Le or Joseph Jankovic.

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Nature Reviews Neurology thanks Rick Helmich, who co-reviewed with Kevin van den Berg; Tau Wu, who co-reviewed with Dongling Zhang; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Li, T., Le, W. & Jankovic, J. Linking the cerebellum to Parkinson disease: an update. Nat Rev Neurol 19, 645–654 (2023). https://doi.org/10.1038/s41582-023-00874-3

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