Downregulated Platelet miR-1233-5p in Patients with Alzheimer's Pathologic Change with Mild Cognitive Impairment is Associated with Abeta-Induced Platelet Activation via P-Selectin

Abstract

MicroRNAs (miRNAs) have been proposed as a promising biomarker for various diseases including Alzheimer's disease (AD). More attention has recently been focused on the diagnosis and treatment at earlier stage of mild cognitive impairment (MCI) for preventing its progression to AD. To identify potential pathologic markers for Abeta(+)MCI (Alzheimer's pathologic change with MCI), we investigated miRNA expression profiles in the platelets from patients with Abeta(+)MCI, in comparison with those from Abeta(-)MCI (Non-Alzheimer's pathologic change with MCI) and CNI (cognitively normal individuals). We found that let-7i-5p, miR-125a, miR-1233-5p, and miR-6787-5p were significantly downregulated, while miR-6880-5p expression was upregulated. Of these, only miR-1233-5p was significantly downregulated by Abeta treatment in both human platelets and their precursor megakaryocytes (MEG-01 cells). We explored the role of miRNAs by using miRNA mimics or inhibitors, and found that the diminished level of miR-1233-5p was associated with Abeta-induced increase in the expression of P-selectin and cell adhesion to fibronectin. Our results further indicated that Abeta-induced increase in platelet/MEG adhesion to fibronectin is likely mediated via P-selectin. In conclusion, this study suggests the downregulation of platelet-derived miR-1233-5p as a pathologic marker for Abeta(+)MCI.