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Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease.
Acta Neuropathol Commun. 2017 Jan 31; 5(1):10.AN

Abstract

MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer's disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors' AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains.

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Authors+Show Affiliations

Hara N
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
Kikuchi M
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
Miyashita A
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
Hatsuta H
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Saito Y
Department of Pathology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan.
Kasuga K
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan. Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
Murayama S
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Ikeuchi T
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
Kuwano R
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan. ryosun@bri.niigata-u.ac.jp. Asahigawaso Research Institute, Asahigawaso Medical-Welfare Center, Okayama, Japan. ryosun@bri.niigata-u.ac.jp. Department of Molecular Genetics, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951-8585, Japan. ryosun@bri.niigata-u.ac.jp.

MeSH

AgedAged, 80 and overAlzheimer DiseaseApolipoproteins EArea Under CurveBiomarkersBrainCell Line, TumorDisease ProgressionFemaleHumansMaleMicroRNAsReverse Transcriptase Polymerase Chain ReactionSensitivity and SpecificitySequence Analysis, RNA

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28137310

Citation

Hara, Norikazu, et al. "Serum microRNA miR-501-3p as a Potential Biomarker Related to the Progression of Alzheimer's Disease." Acta Neuropathologica Communications, vol. 5, no. 1, 2017, p. 10.
Hara N, Kikuchi M, Miyashita A, et al. Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease. Acta Neuropathol Commun. 2017;5(1):10.
Hara, N., Kikuchi, M., Miyashita, A., Hatsuta, H., Saito, Y., Kasuga, K., Murayama, S., Ikeuchi, T., & Kuwano, R. (2017). Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease. Acta Neuropathologica Communications, 5(1), 10. https://doi.org/10.1186/s40478-017-0414-z
Hara N, et al. Serum microRNA miR-501-3p as a Potential Biomarker Related to the Progression of Alzheimer's Disease. Acta Neuropathol Commun. 2017 Jan 31;5(1):10. PubMed PMID: 28137310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease. AU - Hara,Norikazu, AU - Kikuchi,Masataka, AU - Miyashita,Akinori, AU - Hatsuta,Hiroyuki, AU - Saito,Yuko, AU - Kasuga,Kensaku, AU - Murayama,Shigeo, AU - Ikeuchi,Takeshi, AU - Kuwano,Ryozo, Y1 - 2017/01/31/ PY - 2016/12/10/received PY - 2017/01/26/accepted PY - 2017/2/1/entrez PY - 2017/2/1/pubmed PY - 2017/10/27/medline KW - Alzheimer’s disease KW - Autopsied brain KW - Blood-based biomarker KW - Braak staging KW - Next-generation sequencing KW - miR-501-3p KW - microRNA SP - 10 EP - 10 JF - Acta neuropathologica communications JO - Acta Neuropathol Commun VL - 5 IS - 1 N2 - MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer's disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors' AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains. SN - 2051-5960 UR - https://www.unboundmedicine.com/medline/citation/28137310/Serum_microRNA_miR_501_3p_as_a_potential_biomarker_related_to_the_progression_of_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -