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.

Transcriptional and epigenetic phenomena in peripheral blood cells of monozygotic twins discordant for Alzheimer’s disease, a case report / C. D'Addario, S..B. Candia, B. Arosio, M. Di Bartolomeo, C. Abbate, A. Casè, S. Candeletti, P. Romualdi, S. Damanti, M. Maccarrone, L..C. Bergamaschini, D. Mari. - In: JOURNAL OF THE NEUROLOGICAL SCIENCES. - ISSN 0022-510X. - 372(2017 Jan 15), pp. 211-216. [10.1016/j.jns.2016.11.052]

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

B. Arosio;M. Di Bartolomeo;A. Casè;S. Damanti;L..C. Bergamaschini
Penultimo
;
D. Mari
Ultimo
2017

Abstract

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.
monozygotic twins; Alzheimer's disease; peripheral blood mononuclear cells; gene expression; epigenetic mechanisms
Settore MED/09 - Medicina Interna
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/525530
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