| Autor: |
Kmetzsch, Virgilio, Latouche, Morwena, Saracino, Dario, Rinaldi, Daisy, Camuzat, Agnès, Gareau, Thomas, Le Ber, Isabelle, Colliot, Olivier, Becker, Emmanuelle |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.17605/osf.io/4pw8f |
| Popis: |
Several studies have identified circulating microRNAs (miRNAs) as relevant in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), either based on differential expression analyses or classification methods. These two fatal neurodegenerative diseases may be sporadic or genetically determined. Mutations in the C9orf72 gene or in the PGRN gene are among the most common monogenic forms, the former causing FTD and/or ALS and the latter causing FTD. Even though there is converging evidence of the association between miRNA expression levels and FTD and ALS diagnosis, the identified miRNA signatures rarely overlap among studies. One should note that there is an important heterogeneity of the studied cohorts: most of them are sporadic or mixed cohorts of sporadic and genetic forms. More specifically, it is unclear which microRNAs are specific of a given genetic mutation or can be markers in several mutations. It is also unclear if microRNAs identified in sporadic forms are differentially expressed in genetic forms. Furthermore, many of the published studies did not include an independent validation cohort, which may be another source of discrepancy between results. This lack of convergence between different studies so far hinders the use of miRNAs in clinical trials. We intend to test different circulating miRNA signatures identified in the literature in two independent homogeneous cohorts: one focused on C9orf72 mutation carriers and another comprising PGRN mutation carriers. For that purpose, we selected all published papers proposing specific miRNAs, extracted from human plasma or serum, as potential biomarkers of FTD and/or ALS. We will investigate whether (1) miRNAs discovered in cohorts of sporadic patients (or in mixed cohorts with sporadic and genetic forms) may be used as biomarkers in C9orf72 and/or PGRN genetic forms, (2) miRNAs discovered in a C9orf72 cohort may be useful in a PGRN cohort, and (3) miRNAs discovered in a C9orf72 cohort are validated in an independent C9orf72 cohort. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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