@article{10902/32472,
year = {2023},
url = {https://hdl.handle.net/10902/32472},
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.},
organization = {ACKNOWLEDGEMENTS: We thank the patients and their relatives for their generous and continued collaboration in this project. M.F. was funded by María de Maeztu programme (grant #MDM-2017-0729) to the Parkinson’s disease and Movement Disorders group of the Institut de Neurociències (Universitat de Barcelona). S.L. was beneficiary of a PFIS fellowship from Instituto de Salud Carlos III (ISCIII) and co-funded by the European Regional Development Fund (ERDF) (grant #FI18/00221). J.C. was supported by a Miguel Servet grant from Instituto de Salud Carlos III (ISCIII) co-funded by the European Union (grant #CPII18/00026). R.F.-S. was supported by the Miguel Servet (grant #CP19/00048), FIS (grant #FIS20-PI20/00659) and PFIS (grant #FI21/00104) programs from the Instituto de Salud Carlos III (ISCIII) co-funded by the European Union, and also by a Jóvenes Investigadores (JIN) grant of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Agencia Estatal de Investigación (AEI) (AEI/FEDER/UE) (grant #SAF2015-73508-JIN). We also thank the support from the AGAUR program from the Generalitat de Catalunya (grant AGAUR#2017SGR1502) and the Spanish Network for Research on Neurodegenerative Disorders (CIBERNED) —ISCIII (CIBERNED: CB06/05/0018-ISCIII).},
publisher = {Nature Publishing Group},
publisher = {NPJ Parkinson's Disease, 2023, 9, 15},
title = {Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease},
author = {Soto, Marta and Fernández, Manel and Bravo, Paloma and Lahoz, Sara and Garrido, Alicia and Sánchez-Rodríguez, Antonio and Rivera-Sánchez, María and Sierra Peña, María and Melón, Paula and Roig-García, Ana and Naito, Anna and Casey, Bradford and Camps, Jordi and Tolosa, Eduardo and Martí, María José and Infante Ceberio, Jon and Ezquerra, Mario and Fernández-Santiago, Rubén},
}