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Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (<jats:sup>1<\/jats:sup>H-MRS) provide promising non-invasive diagnostic and follow-up tools, also serving to evaluate therapies efficacy. However, pre-clinical studies showing relationship between MRI-MRS based biomarkers and functional performance are missing, which hampers an efficient clinical translation of therapeutics. This study assessed motor behaviour, neurochemical profiles, and morphometry of the cerebellum of MJD transgenic mice and patients aiming at establishing magnetic-resonance-based biomarkers. <jats:sup>1<\/jats:sup>H-MRS and structural MRI measurements of MJD transgenic mice were performed with a 9.4\u00a0Tesla scanner, correlated with motor performance on rotarod and compared with data collected from human patients. We found decreased cerebellar white and grey matter and enlargement of the fourth ventricle in both MJD mice and human patients as compared to controls. <jats:italic>N<\/jats:italic>-acetylaspartate (NAA), NAA\u2009+\u2009<jats:italic>N<\/jats:italic>-acetylaspartylglutamate (NAA\u2009+\u2009NAAG), Glutamate, and Taurine, were significantly decreased in MJD mouse cerebellum regardless of age, whereas myo-Inositol (Ins) was increased at early time-points. Lower neurochemical ratios levels (NAA\/Ins and NAA\/total Choline), previously correlated with worse clinical status in SCAs, were also observed in MJD mice cerebella. NAA, NAA\u2009+\u2009NAAG, Glutamate, and Taurine were also positively correlated with MJD mice motor performance. Importantly, these <jats:sup>1<\/jats:sup>H-MRS results were largely analogous to those found for MJD in human studies and in our pilot data in human patients. We have established a magnetic resonance-based biomarker approach to monitor novel therapies in preclinical studies and human clinical trials.<\/jats:p>","DOI":"10.1186\/s40478-022-01329-4","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T11:02:49Z","timestamp":1647687769000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cerebellar morphometric and spectroscopic biomarkers for Machado-Joseph Disease"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-8108","authenticated-orcid":false,"given":"Catarina Oliveira","family":"Miranda","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5816-2051","authenticated-orcid":false,"given":"Rui Jorge","family":"Nobre","sequence":"additional","affiliation":[]},{"given":"Vitor Hugo","family":"Paiva","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Valente","family":"Duarte","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Castelhano","sequence":"additional","affiliation":[]},{"given":"Lorena Itat\u00ed","family":"Petrella","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9","family":"Sereno","sequence":"additional","affiliation":[]},{"given":"Magda","family":"Santana","sequence":"additional","affiliation":[]},{"given":"S\u00f3nia","family":"Afonso","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Janu\u00e1rio","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Castelo-Branco","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-3307","authenticated-orcid":false,"given":"Lu\u00eds Pereira","family":"de Almeida","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,3,19]]},"reference":[{"key":"1329_CR1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/ng1194-221","volume":"8","author":"Y Kawaguchi","year":"1994","unstructured":"Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S et al (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. 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