{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:32:20Z","timestamp":1783477940921,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids\u2019 serum levels in a cohort of Parkinson\u2019s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients and healthy subjects with (GBA-HC) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn and Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-HC and HC were also considered. Clinical assessment included the Movement Disorder Society revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with the triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-HC (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p &lt; 0.05, Fisher\u2019s exact test) and higher MDS-UPDRS part-II (p &lt; 0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5\u03b1-dihydroprogesterone. Allopregnanolone was the only neurosteroid significantly lower (p &lt; 0.01, Dunn\u2019s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.<\/jats:p>","DOI":"10.3390\/biom14081022","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T03:43:28Z","timestamp":1724039008000},"page":"1022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neurosteroid Levels in GBA Mutated and Non-Mutated Parkinson\u2019s Disease: A Possible Factor Influencing Clinical Phenotype?"],"prefix":"10.3390","volume":"14","author":[{"given":"Francesco","family":"Cavallieri","sequence":"first","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Grisanti","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9234","authenticated-orcid":false,"given":"Edoardo","family":"Monfrini","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Grande Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Fioravanti","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Toschi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Di Rauso","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1856-7422","authenticated-orcid":false,"given":"Jessica","family":"Rossi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-026X","authenticated-orcid":false,"given":"Alessio","family":"Di Fonzo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Grande Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2511","authenticated-orcid":false,"given":"Giuseppe","family":"Biagini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Valzania","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet Lond Engl."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Riboldi, G.M., and Di Fonzo, A.B. 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