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

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Abstract

Plasma 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.

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Acknowledgments

This work is supported by grants CSD2010-00045 and SAF2012-39852 from the Spanish Ministry of Economy and Competitiveness (MINECO) and the European Regional Development Fund (ERDF), Instituto de Salud Carlos III (PI11/03035, PI11/02425, PI14/01561), and a grant from the Fundació la Marató de TV3 (20142610). Marta Cosín-Tomás is supported by a predoctoral fellowship from MINECO (FPU 2013).

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Authors and Affiliations

  1. Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain

    Marta Cosín-Tomás, Coral Sanfeliu & Perla Kaliman

  2. Unitat de Farmacologia, Facultat de Farmàcia, Institut de Neurociències, Universitat de Barcelona and CIBERNED, Barcelona, Spain

    Marta Cosín-Tomás & Mercè Pallàs

  3. Alzheimer’s Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain

    Anna Antonell, Albert Lladó, Raquel Sanchez-Valle & José Luís Molinuevo

  4. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Anna Antonell, Albert Lladó, Mario Ezquerra, Maria José Martí, Raquel Sanchez-Valle, José Luís Molinuevo, Coral Sanfeliu & Perla Kaliman

  5. Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau de Barcelona, Barcelona, Spain

    Daniel Alcolea, Juan Fortea & Albert Lleó

  6. Parkinson’s Disease and Movement Disorders Unit, Institut de Neurociències Hospital Clínic, CIBERNED, Barcelona, Catalonia, Spain

    Mario Ezquerra & Maria José Martí

  7. Center for Mind and Brain, University of California Davis, Davis, CA, USA

    Perla Kaliman

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  1. Marta Cosín-Tomás
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  2. Anna Antonell
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Correspondence to Coral Sanfeliu or Perla Kaliman.

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Subjects were recruited at Hospital Clínic de Barcelona (cohort 1 n = 20–21/group; groups HC, AD, PAD, and PD) and at Hospital de Sant Pau de Barcelona (cohort 2 n = 15/group; groups HC, AD, PAD). All participants gave informed written consent.

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Cosín-Tomás, M., Antonell, A., Lladó, A. et al. Plasma miR-34a-5p and miR-545-3p as Early Biomarkers of Alzheimer’s Disease: Potential and Limitations. Mol Neurobiol 54, 5550–5562 (2017). https://doi.org/10.1007/s12035-016-0088-8

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