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Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease.
Curr Alzheimer Res. 2017; 14(12):1305-1317.CA

Abstract

BACKGROUND

miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD).

METHODS

The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice.

CONCLUSION

These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.

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Authors+Show Affiliations

Arena A
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam. Netherlands.
Iyer AM
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam. Netherlands.
Milenkovic I
Institute of Neurology, Medical University of Vienna. Austria.
Kovacs GG
Institute of Neurology, Medical University of Vienna. Austria.
Ferrer I
Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, Hospitalet de Llobregat. Spain.
Perluigi M
Department of Biochemical Sciences, Sapienza University of Rome, Rome. Italy.
Aronica E
Department of (Neuro) Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam. Netherlands.

MeSH

AdolescentAdultAgedAged, 80 and overAlzheimer DiseaseAnimalsChildChild, PreschoolDisease Models, AnimalDown SyndromeFetusGene Expression Regulation, DevelopmentalGestational AgeGlial Fibrillary Acidic ProteinHippocampusHumansInfantInterleukin-1 Receptor-Associated KinasesInterleukin-1betaMiceMice, TransgenicMicroRNAsMiddle AgedRNA, MessengerTNF Receptor-Associated Factor 6Young Adult

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28720071

Citation

Arena, A, et al. "Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease." Current Alzheimer Research, vol. 14, no. 12, 2017, pp. 1305-1317.
Arena A, Iyer AM, Milenkovic I, et al. Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease. Curr Alzheimer Res. 2017;14(12):1305-1317.
Arena, A., Iyer, A. M., Milenkovic, I., Kovacs, G. G., Ferrer, I., Perluigi, M., & Aronica, E. (2017). Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease. Current Alzheimer Research, 14(12), 1305-1317. https://doi.org/10.2174/1567205014666170706112701
Arena A, et al. Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease. Curr Alzheimer Res. 2017;14(12):1305-1317. PubMed PMID: 28720071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease. AU - Arena,A, AU - Iyer,A M, AU - Milenkovic,I, AU - Kovacs,G G, AU - Ferrer,I, AU - Perluigi,M, AU - Aronica,E, PY - 2017/09/16/received PY - 2017/05/11/revised PY - 2017/05/18/accepted PY - 2017/7/20/pubmed PY - 2018/6/22/medline PY - 2017/7/20/entrez KW - Alzheimer's disease KW - Down's syndrome KW - Hippocampus KW - Ts65Dn- APP/PS1 KW - development KW - microRNAs. SP - 1305 EP - 1317 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 14 IS - 12 N2 - BACKGROUND: miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD). METHODS: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice. CONCLUSION: These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/28720071/Developmental_Expression_and_Dysregulation_of_miR_146a_and_miR_155_in_Down's_Syndrome_and_Mouse_Models_of_Down's_Syndrome_and_Alzheimer's_Disease_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1567-2050&volume=14&issue=12&spage=1305&aulast=Arena DB - PRIME DP - Unbound Medicine ER -