Is Alzheimer disease connected to other immune-mediated disease? Photo: CC-- Hey Paul Studios 05/16/2016 - A number of epidemiological and clinical studies suggest a connection between inflammation and Alzheimer disease, their relationship is not well understood and may have implications for treatment and prevention strategies.

A research team recently set out to figure out if a subset of genes involved with increased risk of inflammation are also associated with increased risk for Alzheimer disease. The research team included JS Yokoyama, Y Wang, AJ Schork, WK Thompson, CM Karch, C Cruchaga, LK McEvoy, A Witoelar, CH Chen, D Holland, JB Brewer, A Franke, WP Dillon, DM Wilson, P Mukherjee, CP Hess, Z Miller, LW Bonham, J Shen, GD Rabinovici, HJ Rosen, BL Miller, BT Hyman, GD Schellenberg, TH Karlsen, OA Andreassen, AM Dale, RS Desikan; and the Alzheimer’s Disease Neuroimaging Initiative.

They are variously affiliated with the Departments of Neurosciences, Cognitive Sciences, Psychiatry, and Radiology at the University of California, San Diego, La Jolla, the Departments of Neurology, Radiology and Biomedical Imaging at the University of California, San Francisco, the Department of Psychiatry, Washington University, St Louis, Missouri, the Division of Mental Health and Addiction, Oslo University Hospital, the Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, the Division of Gastroenterology, and the Norwegian PSC Research Center and KG Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation at Oslo University Hospital Rikshospitalet, Oslo, Norway, the Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany, the Department of Neurology, Massachusetts General Hospital, Boston, and the Department of Pathology and Laboratory Medicine at the University of Pennsylvania Perelman School of Medicine, Philadelphia.

Using data from numerous genome-wide association studies from several clinical research centers, the team conducted a genetic epidemiology study in July 2015, in which they systematically investigated genetic overlap between Alzheimer disease (International Genomics of Alzheimer's Project stage 1) and Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, and psoriasis.

The team assessed P values and odds ratios from genome-wide association studies of more than 100, 000 individuals from previous comparisons of patients vs respective control groups. They used consensus criteria to confirm diagnosis for each disorder previously made in the parent study. The main outcome was the pleiotropic (conjunction) false discovery rate P value.

Follow-up for candidate variants included neuritic plaque and neurofibrillary tangle pathology; longitudinal Alzheimer's Disease Assessment Scale cognitive subscale scores as a measure of cognitive dysfunction (Alzheimer's Disease Neuroimaging Initiative); and gene expression in Alzheimer disease vs control brains (Gene Expression Omnibus data).

These findings confirm genetic overlap between Alzheimer disease and immune-mediated diseases, and suggest that immune system processes influence Alzheimer disease pathogenesis and progression.

For more detail, and exact data results, see JAMA Neurol. 2016 Apr 18. doi: 10.1001/jamaneurol.2016.0150. welcomes your comments below (registration is NOT required).