Abstract
Objective
Despite being one of the most prevalent neurological diseases, the pathophysiology of essential tremor (ET) is not fully understood. Neuropathological studies have identified numerous degenerative changes in the cerebellum of ET patients, however. These data align with considerable clinical and neurophysiological data linking ET to the cerebellum. While neuroimaging studies have variably shown mild atrophy in the cerebellum, marked atrophy is not a clear feature of the cerebellum in ET and a search for a more suitable neuroimaging signature of neurodegeneration is in order. Postmortem studies in ET have examined different neuropathological alterations in the cerebellum, but as of yet have not focused on measures of generalized synaptic markers. This pilot study focuses on synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in practically all synapses in the brain, as a measure of synaptic density in postmortem ET cases.
Methods
The current study utilized autoradiography with the SV2A radioligand [18F]SDM-16 to assess synaptic density in the cerebellar cortex and dentate nucleus in three ET cases and three age-matched controls.
Results
Using [18F]SDM-16, SV2A was 53% and 46% lower in the cerebellar cortex and dentate nucleus, respectively, in ET cases compared to age-matched controls.
Conclusion
In this pilot study, using in vitro SV2A autoradiography, we have observed significantly lower synaptic density in the cerebellar cortex and dentate nucleus of ET cases. Future research could expand on our sample size and focus on in vivo imaging in ET to explore whether SV2A imaging could serve as a much-needed disease biomarker.
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Data Availability
All data can be accessed with reasonable requests.
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Acknowledgements
We thank the staff at the ETCBR in the NYBB and the patients and families that contributed to brain donation.
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NIH: 5R01NS085136-05, UTSW Internal Funding.
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Yanghong, Yang wrote the whole manuscript. Chao, Zheng, and Baosheng, Chen completed the autoradiography experiments. Chao, Zheng helped finalize the autoradiography method and result. Nora Hernandez helped the pathological method and result.
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Yang, Y., Zheng, C., Chen, B. et al. Decreased Synaptic Vesicle Glycoprotein 2A Binding in the Human Postmortem Essential Tremor Cerebellum: Evidence of Reduction in Synaptic Density. Cerebellum 23, 1053–1060 (2024). https://doi.org/10.1007/s12311-023-01611-8
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DOI: https://doi.org/10.1007/s12311-023-01611-8