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Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease

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.

 Fuente: NPJ Parkinson's Disease, 2023, 9, 15

 Editorial: Nature Publishing Group

 Año de publicación: 2023

 Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41531-023-00451-x

 ISSN: 2373-8057

 Proyecto español: SAF2015-73508-JIN

 Url de la publicación: https://doi.org/10.1038/s41531-023-00451-x

Autoría

SOTO, MARTA

FERNÁNDEZ, MANEL

BRAVO, PALOMA

LAHOZ, SARA

GARRIDO, ALICIA

SÁNCHEZ-RODRÍGUEZ, ANTONIO

RIVERA-SÁNCHEZ, MARÍA

MARIA SIERRA PEÑA

MELÓN, PAULA

ROIG-GARCÍA, ANA

NAITO, ANNA

CASEY, BRADFORD

CAMPS, JORDI

TOLOSA, EDUARDO

MARTÍ, MARÍA JOSÉ

EZQUERRA, MARIO

FERNÁNDEZ-SANTIAGO, RUBÉN