TY - JOUR
T1 - MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer's disease
AU - Kumar, Subodh
AU - Vijayan, Murali
AU - Reddy, P. Hemachandra
N1 - Publisher Copyright:
© The Author 2017. Published by Oxford University Press. All rights reserved.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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. Furthermore, human and mouse neuroblastoma cells treated with the amyloid- β(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.
AB - 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. Furthermore, human and mouse neuroblastoma cells treated with the amyloid- β(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.
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U2 - 10.1093/hmg/ddx267
DO - 10.1093/hmg/ddx267
M3 - Article
C2 - 28934394
AN - SCOPUS:85030670779
SN - 0964-6906
VL - 26
SP - 3808
EP - 3822
JO - Human molecular genetics
JF - Human molecular genetics
IS - 19
ER -