High-dose 13.3mg/24h rivastigmine transdermal patch demonstrates efficacy on instrumental activities of daily living: analysis of autonomy and higher-level function subscales

cancelled P2035 Epigenetic mechanisms in a rare case of monozygotic twins discordant for Alzheimer’s disease C. D’Addario1, B. Arosio2, A. Di Francesco1, C. Abbate2, A. Casè3, L. Bergamaschini3,4, D. Mari2, M. Maccarrone1,5 1Biomedical Sciences, University of Teramo, Teramo, 2Geriatric Unit, Department of Clinical Sciences and Community, 3A.S.P. Pio Albergo Trivulzio, 4Medical Sciences, University of Milan, Milan, 5European Center for Brain Research (CERC)/Santa Lucia Foundation, Rome, Italy Case report: Target genes in Alzheimer’s disease (AD) have been identified. The study of rare monozygotic (MZ) twins discordant for AD provides a unique opportunity to evaluate the role of environmental factors in the etiology of the disease. Since epigenetic differences could contribute to phenotypic differences, we investigated either global changes in selected chromatin modifications as well as DNA methylation in peripheral blood mononuclear cells of a couple of these MZ twins. Moreover, we analysed the gene expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) directly recruited by DNMTs. We observed, in the AD twin, markers of transcriptional activation namely a strong reduction in DNA methylation, revealed by higher levels of [3H]methyl group incorporated into DNA (AD twin=2.86±0.23 fold over healthy twin =1±0.16), as well as a clear reduction in histone 3 acetylation at lysine 9 (AD twin=34% versus healthy twin=100%). Consistently, we observed increases in the gene expression of few HDACs isoforms in the AD twin (HDAC2 (3,39), HDAC6 (2,08) HDAC9 (4,16) versus healthy twin =1) and no changes in all the others. Finally, slightly changes were observed in the other histone modifications investigated (Histone 3 Lysine 4 trimethylation, Histone 3 Lysine27 trimethylation) and in all the DNMTs isoforms mRNA levels. Our results unravel epigenetic differences potentially helpful in the understanding of environmental factors and phenotypic differences in MZ twins. We also confirm the use of peripheral blood cells as useful model for the study of gene regulation that mirrors the alterations within the brain.