MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer’s disease

Abstract

The purpose of our study was to identify microRNAs (miRNAs) as early detectable peripheral biomarkers in Alzheimer's disease (AD). To achieve our objective, we assessed miRNAs in serum samples from AD patients and Mild cognitive impairment (MCI) subjects relative to healthy controls. We used Affymetrix microarray analysis and validated differentially expressed miRNAs using qRT-PCR. We further validated miRNA data using AD postmortem brains, amyloid precursor protein transgenic mice and AD cell lines. We identified a gradual upregulation of four miRNAs: miR-455-3p, miR-4668-5p, miR-3613-3p and miR-4674. A fifth miRNA, mir-6722, was down-regulated in persons with AD and mild cognitive impairment compared with controls. Validation analysis by qRT-PCR showed significant upregulation of only miR-455-3p (P = 0.007) and miR-4668-5p (P = 0.016) in AD patients compared with healthy controls. Furthermore, qRT-PCR analysis of the AD postmortem brains with different Braak stages also showed upregulation of miR-455-3p (P = 0.016). However, receiver operating characteristic curves (ROC) curve analysis revealed a significant area under curve (AUC) value only for miR-455-3p in the serum (AUROC = 0.79; P = 0.015) and brains (AUROC = 0.86; P = 0.016) of AD patients. Expression analysis of amyloid precursor protein transgenic mice also revealed high level of mmu-miR-455-3p (P = 0.004) in the cerebral cortex (AD-affected) region of brain and low in the non-affected area, i.e. cerebellum. Further…