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Studies in transgenic mice suggested abnormal cholinergic transmission in the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms.<\/jats:p>","DOI":"10.1093\/brain\/awaa465","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T13:13:52Z","timestamp":1608815632000},"page":"909-923","source":"Crossref","is-referenced-by-count":34,"title":["Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia"],"prefix":"10.1093","volume":"144","author":[{"given":"Joachim","family":"Mazere","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, CHU de Bordeaux, France"},{"name":"Institute of Cognitive and Integrative Neurosciences, CNRS UMR 5287, Bordeaux University, F33000, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixente","family":"Dilharreguy","sequence":"additional","affiliation":[{"name":"Institute of Cognitive and 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