15/01/15 22.24 Rheumatoid Arthritis and Alzheimer’s Disease: Genetic and Epigenetic…nflammatory Regulation - Gianfranco Ferraccioli - Discovery Medicine Page 1 of 11 http://www.discoverymedicine.com/Gianfranco-Ferraccioli/2012/12/24…s-disease-genetic-and-epigenetic-links-in-inflammatory-regulation/ Access PDF as a Subscriber Purchase/Download This Related Articles Email This Article Share This Article January 15, 2015 Medical Specialties Life Sciences Species and Cell Types Research Technology Therapeutic Technology and Methodology Pharmaceutical and Healthcare Industry Article Published in the Author Account of Gianfranco Ferraccioli Rheumatoid Arthritis and Alzheimer’s Disease: Genetic and Epigenetic Links in Inflammatory Regulation Published on December 24, 2012 Author: Gianfranco Ferraccioli Specialty: Rheumatology , Internal Medicine , Immunology Institution: Divisions of Rheumatology and Internal Medicine, Institute of Rheumatology and Affine Sciences, School of Medicine, Catholic University of the Sacred Heart Address: Rome, 00168, Italy Author: Angela Carbonella Specialty: Rheumatology Institution: Division of Rheumatology, Institute of Rheumatology and Affine Sciences, School of Medicine, Catholic University of the Sacred Heart Address: Rome, 00168, Italy Author: Elisa Gremese Specialty: Rheumatology Institution: Division of Rheumatology, Institute of Rheumatology and Affine Sciences, School of Medicine, Catholic University of the Sacred Heart Address: Rome, 00168, Italy Author: Stefano Alivernini Specialty: Rheumatology Institution: Division of Rheumatology, Institute of Rheumatology and Affine Sciences, School of Medicine, Catholic University of the Sacred Heart Address: Rome, 00168, Italy Abstract: Controversial data are available about the relationship between Alzheimer's disease (AD) and rheumatoid arthritis (RA). An inverse relationship between AD and RA, due to different factors, was previously described. Similarly to RA, AD pathogenesis is multifactorial and different findings support the inflammatory pathogenetic hypothesis. Several inflammatory mediators are involved in the disease onset and progression regulated by genetic and epigenetic mechanisms. Among them, inteleukin-6 (IL-6) and interleukin-1 (IL-1) as pro-inflammatory soluble factors produced by monocytes-macrophages and tumor necrosis factor alpha (TNF-!) produced by activated macrophages and mononuclear cells represent key molecules in the induction and maintenance of chronic inflammation in RA. In particular a link with the T allele of the SNP 3953 T/C in the IL-1 gene and an overexpression of miR-146a appears to be common to both RA and AD. In this review we will discuss the genetic and epigenetic regulation of the inflammatory cascade in RA and AD to find out the possible links between RA and AD onset. Introduction An inverse relationship between Alzheimer’s disease (AD) and rheumatoid arthritis (RA) has been reported since the early 1990’s. A reduced prevalence of AD has been described in long-using non-steroidal anti-inflammatory agents (NSAIDs ) RA patients analyzed in a post-mortem survey (McGeer et al., 1990). The incidence of RA in Home Contact Help Author Services Author Log In Subscriber Services Subscriber Log In About About the Author