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Title

Plasma miR-34a-5p and miR-545-3p as Early Biomarkers of Alzheimer’s Disease: Potential and Limitations

AuthorsCosín-Tomás, Marta; Antonell, Anna; Lladó, Albert; Alcolea, Daniel; Fortea, Juan; Ezquerra, Mario; Lleó, Alberto; Martí, María-José; Pallàs, Mercè; Sánchez-Valle, Raquel; Molinuevo, José L.; Sanfeliu, Coral ; Kaliman, Perla
KeywordsmiRNA
Alzheimer’s disease
Plasma biomarker
Preclinical
miR-34a-5p
miR-545-3p
Issue DateSep-2017
PublisherSpringer
CitationMolecular Neurobiology 54(7): 5550-5562 (2017)
AbstractPlasma microRNAs (miRNAs) have been proposed as potential biomarkers in Alzheimer’s disease (AD). Here, we explored their use as early sensors of the preclinical phase of the disease, when brain pathology is being developed and no cognitive loss is detected. For this purpose, we analyzed a set of ten mature plasma miRNAs in symptomatic patients with AD from a cohort that also included healthy controls (HC) and patients with preclinical Alzheimer’s disease (PAD) (cohort 1). Plasmas from subjects with Parkinson’s disease (PD) were used to control for disease specificity. We found that miR-15b-5p, miR-34a-5p, miR-142-3p, and miR-545-3p levels significantly distinguished AD from PD and HC subjects. We next examined the expression of these four miRNAs in plasma from subjects with PAD. Among these, miR-34a-5p and miR-545-3p presented good diagnostic accuracy to distinguish both AD and PAD from HC subjects, according to the receiver operating characteristic (ROC) curve analysis. Both miRNAs also demonstrated a significant positive correlation with Aβ1–42 levels in cerebrospinal fluid (CSF). Taking into account the clinical potential of these findings, we decided to validate the diagnostic accuracy of miR-34a-5p and miR-545-3p in plasma samples from an independent cohort (cohort 2), in which we did not observe the alterations described by us and others in AD and PAD samples. Although miR-34a-5p and miR-545-3p might be promising early biomarker candidates for AD, our study highlights possible sources of variability in miRNA analysis across hospitals, which currently prevents their use as reliable clinical tools.
Publisher version (URL)https://doi.org/10.1007/s12035-016-0088-8
URIhttp://hdl.handle.net/10261/176879
DOI10.1007/s12035-016-0088-8
ISSN0893-7648
E-ISSN1559-1182
Appears in Collections:(IIBB) Artículos
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