Transcriptional and epigenetic phenomena in peripheral blood cells of monozygotic twins discordant for alzheimer's disease, a case report

被引:21
作者
D'Addario, Claudio [1 ,2 ]
Candia, Sussy Bastias [3 ]
Arosio, Beatrice [4 ,5 ]
Di Bartolomeo, Martina [1 ]
Abbate, Carlo [5 ]
Case, Alessandra [4 ]
Candeletti, Sanzio [6 ]
Romualdi, Patrizia [6 ]
Damanti, Sarah [5 ,7 ]
Maccarrone, Mauro [2 ,8 ]
Bergamaschini, Luigi [4 ,9 ]
Mari, Daniela [4 ,5 ]
机构
[1] Univ Teramo, Fac Biosci & Technol Food Agr & Environm, Via Renato Balzarini 1, I-64100 Teramo, Italy
[2] Santa Lucia Fdn, European Ctr Brain Res CERC, Rome, Italy
[3] Univ Tarapaca, Fac Ciencias, Dept Biol, Arica, Chile
[4] Univ Milan, Geriatr Unit, Dept Med Sci & Community Hlth, I-20122 Milan, Italy
[5] IRCCS Osped Maggiore Policlin, Fdn Ca Granda, Milan, Italy
[6] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy
[7] Univ Milan, Nutr Sci, Milan, Italy
[8] Campus Biomed Univ Rome, Dept Med, Rome, Italy
[9] ASP Pio Albergo Trivulzio, Milan, Italy
关键词
Monozygotic twins; Alzheimer's disease; Peripheral blood mononuclear cells; Gene expression; Epigenetic mechanisms; DNA METHYLATION; CEREBROSPINAL-FLUID; NORMATIVE VALUES; GENE; BIOMARKERS; DIAGNOSIS; PROMOTER; RISK; APOE;
D O I
10.1016/j.jns.2016.11.052
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Target genes in Alzheimer's disease (AD) have been identified. In monozygotic twins discordant for AD we analysed the expression of selected genes, and their possible regulation by epigenetic mechanisms in peripheral blood mononuclear cells, possibly useful to discover biomarkers. Amyloid precursor protein, sirtuin 1 and peptidyl prolyl isomerase 1 gene expressions were highly up-regulated in the AD twin versus the healthy one. Consistently with sirtuin 1 role in controlling acetylation status, we observed a substantial reduction of the acetylation on histone 3 lysine 9, associated with gene transcription in the AD twin. Noteworthy in the AD twin we also observed an increased gene expression in two histone deacetylases (HDACs) isoforms: HDAC2 and HDAC9. A general DNA hypomethylation of all gene promoters studied was also observed in both twins. Our results unravel transcriptional and epigenetic differences potentially helpful to better understand environmental factors and phenotypic differences in monozygotic twins. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:211 / 216
页数:6
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