Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson’s disease Article Swipe
Marta Soto
,
Manel Fernández
,
Paloma Bravo
,
Sara Lahoz
,
Alícia Garrido
,
Antonio Sánchez‐Rodríguez
,
María Rivera‐Sánchez
,
María Sierra
,
Paula Melón
,
Ana Roig-García
,
Anna Naito
,
Bradford Casey
,
Jordi Camps
,
Eduardo Tolosa
,
María‐José Martí
,
Jon Infante
,
Mario Ezquerra
,
Rubén Fernández‐Santiago
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41531-023-00451-x
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41531-023-00451-x
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.
Related Topics
Concepts
LRRK2
microRNA
Dopamine transporter
Internal medicine
Cohort
Parkinson's disease
Disease
Oncology
Biology
Medicine
Dopaminergic
Genetics
Gene
Dopamine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41531-023-00451-x
- https://www.nature.com/articles/s41531-023-00451-x.pdf
- OA Status
- gold
- Cited By
- 10
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4319007318
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4319007318Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41531-023-00451-xDigital Object Identifier
- Title
-
Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson’s diseaseWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-02-02Full publication date if available
- Authors
-
Marta Soto, Manel Fernández, Paloma Bravo, Sara Lahoz, Alícia Garrido, Antonio Sánchez‐Rodríguez, María Rivera‐Sánchez, María Sierra, Paula Melón, Ana Roig-García, Anna Naito, Bradford Casey, Jordi Camps, Eduardo Tolosa, María‐José Martí, Jon Infante, Mario Ezquerra, Rubén Fernández‐SantiagoList of authors in order
- Landing page
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https://doi.org/10.1038/s41531-023-00451-xPublisher landing page
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https://www.nature.com/articles/s41531-023-00451-x.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://www.nature.com/articles/s41531-023-00451-x.pdfDirect OA link when available
- Concepts
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LRRK2, microRNA, Dopamine transporter, Internal medicine, Cohort, Parkinson's disease, Disease, Oncology, Biology, Medicine, Dopaminergic, Genetics, Gene, DopamineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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10Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 5, 2023: 3Per-year citation counts (last 5 years)
- References (count)
-
63Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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