MiRNA-501-3p and MiRNA-502-3p: A promising biomarker panel for Alzheimer's disease.

INTRODUCTION

Alzheimer's disease (AD) lacks a less invasive and early detectable biomarker. Here, we investigated the biomarker potential of miR-501-3p and miR-502-3p using different AD sources.

METHODS

MiR-501-3p and miR-502-3p expressions were evaluated in AD cerebrospinal fluid (CSF) exosomes, serum exosomes, familial and sporadic AD fibroblasts and B-lymphocytes by qRT-PCR analysis. Further, miR-501-3p and miR-502-3p expressions were analysed in APP, Tau plasmid transfected cells media exosomes and in different brain cell types.

RESULTS

MiR-501-3p and miR-502-3p expressions were significantly up-regulated in AD CSF exosomes relative to controls. MiRNA levels were high in accordance with amyloid plaque and NFT density in multiple brain regions. Similarly, both miRNAs were elevated in AD and MCI serum exosomes compared with controls. MiR-502-3p expression was high in familial AD and sporadic AD B-lymphocytes. MiR-501-3p and miR-502-3p expression were elevated intracellularly and secreted extracellularly in response to APP and Tau pathology. Finally, neurons and astrocytes displayed high expression of these miRNAs.

DISCUSSION: These results suggest that miR-501-3p and miR-502-3p could be promising biomarkers for AD.

KEY POINTS: MiR-501-3p and miR-502-3p expression is elevated in AD CSF exosomes, AD serum exosomes, AD B-lymphocytes and Aβ- and Tau-treated cells. MiR-501-3p and miR-502-3p are correlated with amyloid plaque and NFT tangle density in specific brain regions. MiR-501-3p and miR-502-3p are highly expressed in neurons and astrocytes, suggesting that these cells are the source of miRNA secretion. MiR-501-3p and miR-502-3p could be a promising biomarker panel for AD.