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Protein aggregation and neuronal morphology were evaluated using fluorescent microscopy. Mitochondrial respiration was measured using the Seahorse Analyzer. The multi\u2010electrode array (MEA) was used to identify network activity. Finally, gene expression changes were studied using RNA\u2010seq to identify disease\u2010specific mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bioenergetics deficits in patient\u2010derived fibroblasts and SCA1 neuronal cultures showed altered oxygen consumption rate, suggesting involvement of mitochondrial dysfunction in SCA1. In SCA1 hiPSC\u2010derived neuronal cells, nuclear and cytoplasmic aggregates were identified similar in localization as aggregates in SCA1 postmortem brain tissue. SCA1 hiPSC\u2010derived neuronal cells showed reduced dendrite length and number of branching points while MEA recordings identified delayed development in network activity in SCA1 hiPSC\u2010derived neuronal cells. Transcriptome analysis identified 1050 differentially expressed genes in SCA1 hiPSC\u2010derived neuronal cells associated with synapse organization and neuron projection guidance, where a subgroup of 151 genes was highly associated with SCA1 phenotypes and linked to SCA1 relevant signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patient\u2010derived cells recapitulate key pathological features of SCA1 pathogenesis providing a valuable tool for the identification of novel disease\u2010specific processes. This model can be used for high throughput screenings to identify compounds, which may prevent or rescue neurodegeneration in this devastating disease. \u00a9 2023 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29446","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T22:10:05Z","timestamp":1686175805000},"page":"1428-1442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Spinocerebellar Ataxia Type 1 Characteristics in Patient\u2010Derived Fibroblast and <scp>iPSC<\/scp>\u2010Derived Neuronal Cultures"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9722-8110","authenticated-orcid":false,"given":"Ronald A.M.","family":"Buijsen","sequence":"first","affiliation":[{"name":"Department of 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