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MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer's disease.
Hum Mol Genet. 2017 10 01; 26(19):3808-3822.HM

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. 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 Aβ pathologies unveiled its biomarker characteristics and a precise role in AD pathogenesis.

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Authors+Show Affiliations

Kumar S
Biomarker Unit, Garrison Institute on Aging.
Vijayan M
Biomarker Unit, Garrison Institute on Aging.
Reddy PH
Biomarker Unit, Garrison Institute on Aging. Department of Cell Biology & Biochemistry. Department of Pharmacology & Neuroscience. Department of Neurology. Department of Speech, Language and Hearing Sciences. Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

MeSH

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsAutopsyBiomarkersCase-Control StudiesCell LineCognitive DysfunctionFemaleGene Expression ProfilingHumansMaleMiceMice, TransgenicMicroRNAsMiddle Aged

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28934394

Citation

Kumar, Subodh, et al. "MicroRNA-455-3p as a Potential Peripheral Biomarker for Alzheimer's Disease." Human Molecular Genetics, vol. 26, no. 19, 2017, pp. 3808-3822.
Kumar S, Vijayan M, Reddy PH. MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer's disease. Hum Mol Genet. 2017;26(19):3808-3822.
Kumar, S., Vijayan, M., & Reddy, P. H. (2017). MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer's disease. Human Molecular Genetics, 26(19), 3808-3822. https://doi.org/10.1093/hmg/ddx267
Kumar S, Vijayan M, Reddy PH. MicroRNA-455-3p as a Potential Peripheral Biomarker for Alzheimer's Disease. Hum Mol Genet. 2017 10 1;26(19):3808-3822. PubMed PMID: 28934394.
* Article titles in AMA citation format should be in sentence-case
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, PY - 2017/05/04/received PY - 2017/07/04/accepted PY - 2017/9/22/entrez PY - 2017/9/22/pubmed PY - 2018/1/24/medline SP - 3808 EP - 3822 JF - Human molecular genetics JO - Hum Mol Genet VL - 26 IS - 19 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 Aβ pathologies unveiled its biomarker characteristics and a precise role in AD pathogenesis. SN - 1460-2083 UR - https://www.unboundmedicine.com/medline/citation/28934394/MicroRNA_455_3p_as_a_potential_peripheral_biomarker_for_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -