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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 [ 18 F]SDM-16 to assess synaptic density in the cerebellar cortex and dentate nucleus in three ET cases and three age-matched controls.

Results: Using [ 18 F]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.

Titel:	Decreased Synaptic Vesicle Glycoprotein 2A Binding in the Human Postmortem Essential Tremor Cerebellum: Evidence of Reduction in Synaptic Density.
Autor/in / Beteiligte Person:	Yang, Y ; Zheng, C ; Chen, B ; Hernandez, NC ; Faust, PL ; Cai, Z ; Louis, ED ; Matuskey, D
Zeitschrift:	Cerebellum (London, England), Jg. 23 (2024-06-01), Heft 3, S. 1053-1060
Veröffentlichung:	<2006->: New York : Springer ; <i>Original Publication</i>: London : Martin Dunitz, c2002-, 2024
Medientyp:	academicJournal
ISSN:	1473-4230 (electronic)
DOI:	10.1007/s12311-023-01611-8
Schlagwort:	Humans Male Aged Female Aged, 80 and over Pilot Projects Autoradiography Middle Aged Autopsy Essential Tremor metabolism Essential Tremor pathology Nerve Tissue Proteins metabolism Synapses metabolism Synapses pathology Membrane Glycoproteins metabolism Cerebellum metabolism Cerebellum pathology Cerebellum diagnostic imaging
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Cerebellum] 2024 Jun; Vol. 23 (3), pp. 1053-1060. <i>Date of Electronic Publication: </i>2023 Oct 03. MeSH Terms: Essential Tremor* / metabolism ; Essential Tremor* / pathology ; Nerve Tissue Proteins* / metabolism ; Synapses* / metabolism ; Synapses* / pathology ; Membrane Glycoproteins* / metabolism ; Cerebellum* / metabolism ; Cerebellum* / pathology ; Cerebellum* / diagnostic imaging ; Humans ; Male ; Aged ; Female ; Aged, 80 and over ; Pilot Projects ; Autoradiography ; Middle Aged ; Autopsy Comments: Update of: Res Sq. 2023 May 02;:. (PMID: 37205584) References: Louis ED, Ottman R. How many people in the USA have essential tremor? Deriving a population estimate based on epidemiological data. Tremor Other Hyperkinet Mov (N Y). 2014;4:259. https://doi.org/10.7916/D8TT4P4B . (PMID: 10.7916/D8TT4P4B25157323) ; Louis ED, McCreary M. How Common is Essential Tremor? 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Acta Neuropathol. 2023. https://doi.org/10.1007/s00401-022-02535-z . (PMID: 10.1007/s00401-022-02535-z3733534210461794) ; Tikoo S, Pietracupa S, Tommasin S, Bologna M, Petsas N, Bharti K, et al. Functional disconnection of the dentate nucleus in essential tremor. J Neurol. 2020;267(5):1358–67. https://doi.org/10.1007/s00415-020-09711-9 . (PMID: 10.1007/s00415-020-09711-931974808) Grant Information: 5R01NS085136-05 United States GF NIH HHS Contributed Indexing: Keywords: Autoradiography; Cerebellum; Essential tremor; Postmortem; Synaptic vesicle glycoprotein 2A; [F18]SDM16 Substance Nomenclature: 0 (SV2A protein, human) Entry Date(s): Date Created: 20231002 Date Completed: 20240518 Latest Revision: 20240524 Update Code: 20240524

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Decreased Synaptic Vesicle Glycoprotein 2A Binding in the Human Postmortem Essential Tremor Cerebellum: Evidence of Reduction in Synaptic Density.