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Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer's disease

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dc.creator Dakterzada, Farida
dc.creator Targa, Adriano
dc.creator Benítez, Iván
dc.creator Romero El Khayat, Leila
dc.creator de Gonzalo Calvo, David
dc.creator Torres, Gerard
dc.creator Moncusí Moix, Anna
dc.creator Huerto Vilas, Raquel
dc.creator Sánchez de la Torre, Manuel
dc.creator Barbé Illa, Ferran
dc.creator Piñol Ripoll, Gerard
dc.date 2020
dc.date.accessioned 2025-11-03T12:15:40Z
dc.date.available 2025-11-03T12:15:40Z
dc.identifier https://doi.org/10.1186/s13195-020-00735-x
dc.identifier 1758-9193
dc.identifier http://hdl.handle.net/10459.1/83231
dc.identifier.uri http://fima-docencia.ub.edu:8080/xmlui/handle/123456789/24209
dc.description Background. MicroRNAs (miRNAs) are noncoding RNAs that are highly relevant as disease biomarkers. Several studies that explored the role of miRNAs in Alzheimer’s disease (AD) demonstrated their usefulness in clinical identification. Nevertheless, miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in AD. The objective of the study was to identify miRNAs that can be used as ECs in AD. Methods. We evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini-Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aβ42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 subjects without AD or any kind of dementia and negative for all core CSF biomarkers of AD, 25 subjects with MCI and negative for CSF biomarkers (MCI −), 22 subjects with MCI and positive for CSF biomarkers (MCI +), and 55 subjects with AD and positive for CSF biomarkers. In the discovery cohort, a profile of 384 miRNAs was determined in the plasma by TaqMan low-density array. The best EC candidates were identified by mean-centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper, and NormFinder algorithms. Results. Nine miRNAs (hsa-miR-324-5p, hsa-miR-22-5p, hsa-miR-103a-2-5p, hsa-miR-362-5p, hsa-miR-425-3p, hsa-miR-423-5p, hsa-let-7i-3p, hsa-miR-532-5p, and hsa-miR-1301-3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa-miR-103a-2-5p was the best EC, followed by hsa-miR-22-5p, hsa-miR-1301-3p, and hsa-miR-425-3p, which had similar stability values in all three algorithms. Conclusions. We identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment.
dc.description Generalitat of Catalonia, Department of Health (PERIS 2019 SLT008/18/00050), and “Fundació La Marató TV3” (464/C/2014) to GPR. This study was cofinanced by FEDER funds from the European Union (“A way to build Europe”). IRBLleida is a CERCA Programme/Generalitat of Catalonia. FD was supported by the Agency for Management of University and Research Grants (FI_B100153). David de Gonzalo Calvo acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII); Miguel Servet 2020: CP20/00041, co-funded by the European Social Fund (ESF)/“Investing in your future”.
dc.language eng
dc.publisher BCM
dc.relation Reproducció del document publicat a: https://doi.org/10.1186/s13195-020-00735-x
dc.relation Alzheimer's Research & Therapy, 2020, vol.12
dc.rights cc-by (c) Authors, 2020
dc.rights info:eu-repo/semantics/openAccess
dc.rights http://creativecommons.org/licenses/by/4.0/
dc.subject Alzheimer’s disease
dc.subject Biomarkers
dc.subject Mild cognitive impairment
dc.subject miRNAs
dc.subject Normalization
dc.subject qPCR
dc.title Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer's disease
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion


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