{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Soto M"],"funding":["Generalitat de Catalunya","Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)","Ministerio de Economía, Industria y Competitividad, Gobierno de España (Ministerio de Economía, Industria y Competitividad)","Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)","Ministry of Economy and Competitiveness | Instituto de Salud Carlos III","Ministerio de Economía, Industria y Competitividad, Gobierno de España","Generalitat de Catalunya (Government of Catalonia)","Ministry of Economy and Competitiveness | Agencia Estatal de Investigación","Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)","Michael J. Fox Foundation for Parkinson’s Research"],"pagination":["15"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9894906"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson's disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers (L2NMC) are at PD high risk but predicting pheno-conversion is challenging given the lack of progression biomarkers. To investigate novel biomarkers for PD premotor stages, we performed a longitudinal microRNA (miRNA) assessment of serum samples from G2019S L2NMC followed-up over 8 years. Our cohort consisted of G2019S L2NMC stratified by dopamine transporter single-photon emission computed tomography (DaT-SPECT) into DaT-negative (n = 20) and DaT-positive L2NMC (n = 20), pheno-converted G2019S L2PD patients (n = 20), idiopathic PD (iPD) (n = 19), and controls (n = 40). We also screened a second cohort of L2PD patients (n = 19) and controls (n = 20) (Total n = 158). Compared to healthy controls, we identified eight deregulated miRNAs in DaT-negative L2NMC, six in DaT-positive L2NMC, and one in L2PD. Between groups, the highest miRNA differences, 24 candidate miRNAs, occurred between DaT-positive L2NMC and L2PD. Longitudinally, we found 11 common miRNAs with sustained variation in DaT-negative and DaT-positive L2NMCs compared to their baselines. Our study identifies novel miRNA alterations in premotor stages of PD co-occurring with progressive DaT-SPECT decline before motor manifestation, whose deregulation seems to attenuate after the diagnosis of L2PD. Moreover, we identified four miRNAs with relatively high discriminative ability (AUC = 0.82) between non-pheno-converted DaT-positive G2019S carriers and pheno-converted L2PD patients (miR-4505, miR-8069, miR-6125, and miR-451a), which hold potential as early progression biomarkers for PD."],"journal":["NPJ Parkinson's disease"],"pubmed_title":["Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease."],"pmcid":["PMC9894906"],"funding_grant_id":["#SAF2015-73508-JIN","#CPII18/00026","AGAUR#2017SGR1502","#CP19/00048","#11849","#FI21/00104","#MDM-2017-0729","CB06/05/0018-ISCIII","#FI18/00221","#FIS20-PI20/00659"],"pubmed_authors":["Casey B","Camps J","Fernandez M","Tolosa E","Infante J","Garrido A","Sanchez-Rodriguez A","Roig-Garcia A","Bravo P","Soto M","Fernandez-Santiago R","Rivera-Sanchez M","Naito A","Marti MJ","Ezquerra M","Sierra M","Lahoz S","Melon P"],"additional_accession":[]},"is_claimable":false,"name":"Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease.","description":"The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson's disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers (L2NMC) are at PD high risk but predicting pheno-conversion is challenging given the lack of progression biomarkers. To investigate novel biomarkers for PD premotor stages, we performed a longitudinal microRNA (miRNA) assessment of serum samples from G2019S L2NMC followed-up over 8 years. Our cohort consisted of G2019S L2NMC stratified by dopamine transporter single-photon emission computed tomography (DaT-SPECT) into DaT-negative (n = 20) and DaT-positive L2NMC (n = 20), pheno-converted G2019S L2PD patients (n = 20), idiopathic PD (iPD) (n = 19), and controls (n = 40). We also screened a second cohort of L2PD patients (n = 19) and controls (n = 20) (Total n = 158). Compared to healthy controls, we identified eight deregulated miRNAs in DaT-negative L2NMC, six in DaT-positive L2NMC, and one in L2PD. Between groups, the highest miRNA differences, 24 candidate miRNAs, occurred between DaT-positive L2NMC and L2PD. Longitudinally, we found 11 common miRNAs with sustained variation in DaT-negative and DaT-positive L2NMCs compared to their baselines. Our study identifies novel miRNA alterations in premotor stages of PD co-occurring with progressive DaT-SPECT decline before motor manifestation, whose deregulation seems to attenuate after the diagnosis of L2PD. Moreover, we identified four miRNAs with relatively high discriminative ability (AUC = 0.82) between non-pheno-converted DaT-positive G2019S carriers and pheno-converted L2PD patients (miR-4505, miR-8069, miR-6125, and miR-451a), which hold potential as early progression biomarkers for PD.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-03-17T15:43:41.2Z","creation":"2025-04-06T14:06:04.49Z"},"accession":"S-EPMC9894906","cross_references":{"pubmed":["36732514"],"doi":["10.1038/s41531-023-00451-x"]}}