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

被引:136
|
作者
Kumar, Subodh [1 ]
Vijayan, Murali [1 ]
Reddy, P. Hemachandra [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Biomarker Unit,Garrison Inst Aging, Lubbock, TX 79430 USA
[2] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA
[3] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA
[4] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Dept Neurol, Lubbock, TX 79430 USA
[5] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Dept Speech Language & Hearing Sci, Lubbock, TX 79430 USA
[6] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Dept Publ Hlth, Lubbock, TX 79430 USA
关键词
AMYLOID-BETA; EXPRESSION; DIAGNOSIS; PLASMA; MIRNA; RISK;
D O I
10.1093/hmg/ddx267
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-36133p 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-46685p (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. Furthermore, human and mouse neuroblastoma cells treated with the amyloid- b(1-42) peptide also showed a similarly higher expression of miR-455-3p. Functional analysis of differentially expressed miRNAs via the miR-path indicated that miR-455-3p was associated in the regulation of several biological pathways. Genes associated with these pathways were found to have a crucial role in AD pathogenesis. An increase in miR-455-3p expression found in AD patients and Ab pathologies unveiled its biomarker characteristics and a precise role in AD pathogenesis.
引用
收藏
页码:3808 / 3822
页数:15
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