Consortium Structure

The leading members of the EPI-AD consortium are all specialized research institutes engaged in clinical and fundamental neuroscience. The added value of this consortium arises from the auspicious cooperation between various experts in the fields of research on epigenetics in aging and AD. As such, research approaches with different levels of complexity (from epidemiology, biochemistry and molecular [epi]genetics to systems biology and bioinformatics) are represented in the various WPs. In line with this, all key resources are shared within the research and training network. Several PIs of this consortium have only recently been appointed to new positions at the beneficiaries where they will establish new techniques or start novel lines of research. The WP descriptions, secondments and joint publications between partners testify to the strong integration of the consortium. Of note, both male and female scientists play a prominent role within the EPI-AD consortium (core members: 10 males, 5 females).


The proposed project is based upon an ongoing successful collaboration between various groups at Maastricht University, the University of Exeter (Exeter, UK), the University of Würzburg (Würzburg, Germany), and the Banner Sun Health Research Institute (BSHRI; AZ, USA). It involves a multidisciplinary research team of psychologists, psychiatrists, molecular biologists, and bioinformaticians. The fruitful collaboration between these groups is illustrated by the various (6) joint PhD theses that have been produced over the past 3 years. The group in Maastricht (D. van den Hove, B. Rutten, P. Aalten, F. Verhey, J. Kleinjans, H. Steinbusch, H. Jacobs, G. Kenis, and N. Senden) focuses on unravelling the interdependent relationship between molecular and neurobiological mechanisms using interdisciplinary and translational research strategies and thus is well-known for its translational projects on AD and epigenetics, as well as for the successful coordination of large European consortia within FP6 and FP7. At the laboratory in Würzburg (T. Haaf, K-P. Lesch, G. Ortega), state-of-the-art molecular biology technology for screening (epi)genetic variation has been developed. In addition, both Maastricht and Würzburg have an outstanding reputation in studying the 5-HT and NA systems. Exeter (K. Lunnon, J. Mill) represents a pioneering epigenetics laboratory, known for its functional annotation of tissue-specific epigenetic variation (across brain and blood), particularly in AD, and high-throughput (hydroxy)methylation profiling and associated bioinformatics analysis.

In addition, the groups led by Dr. A. Ramirez at the Rheinische Friedrich-Wilhelms-Universität Bonn and Prof. Dr. M. Wagner at the DZNE in Bonn (Germany) represent centres of excellence for dementia research, focusing on psychiatric genetics, neuropsychology, neuroimaging in old age, and statistical modelling, with applications in clinical and epidemiological research, which will provide an additional translational perspective to the current proposal. Barcelona (M. Esteller, R. Delgado Morales) represents one of the pioneering European epigenetics groups and one of the first to apply genome-wide analysis of epigenetic profiles in the human brain, contributing to unravelling the role of epigenetic processes on aging and neurodegenerative diseases such as AD. In addition, the group in Barcelona is able to profit from the invaluable insights from Dr. Raya’s laboratory, one of the worldwide pioneers on human iPSC generation and reprogramming. The LCSB in Luxembourg (A. del Sol, E. Glaab) analyses complex neurodegenerative disorders by modelling them as perturbations in molecular networks and cellular pathways. The centre has published a broad set of new bioinformatics tools for pathway and network analysis of omics data, which have been used for the integrated analysis of high-throughput datasets from human and animal AD studies. Recently, the LCSB participated in AD-related international data mining challenges, including the Geoffrey Beene Global Neurodiscovery Challenge (1st place). Of note, GenomeScan (Leiden, the Netherlands) will provide services supporting the EPIC workflow, in close collaboration with Cambridge Epigenetix (Cambridge, UK), Maastricht and Exeter.

Added value

The involvement of every partner within the EPI-AD consortium is crucial for enabling pivotal advances in the development of novel therapeutic approaches for AD. As such, each partner provides its own, specific and complementary contribution, in terms of scientific and technological expertise or available tissue samples (brain-blood-DNA) and related datasets. For instance, Maastricht, next to coordinating the project, contributes by providing tissue and data on the PSI cohort, whereas Exeter and Sun City supply brain and blood tissue and data from AD patients and age-matched controls as well as extensive bioinformatics tools. New York provides all necessary state-of-the-art LCM facilities, whereas Würzburg enables the use of LDBS, thereby only requiring DNA from a limited number of cells. Bonn contributes by means of the AgeCoDe cohort, including longitudinal data ranging from cognitively normal to dementia within the same individual. In close collaboration, Maastricht, Exeter and Luxembourg form a state-of-the-art, systems biology bioinformatics platform, including an efficient high performance computing infrastructure and analysis pipeline for large-scale omics data analysis, allowing novel computational and mathematical modelling of the complex, multidisciplinary datasets generated by this project. Barcelona provides all necessary advanced iPSC technology. Although all these assets are already very valuable in isolation, integrating them into this EPI-AD framework will yield a profound synergistic effect, providing a true translational approach, ranging from the discovery of biomarkers to acquiring novel insights into the pathophysiology of AD, as well as the generation of a novel advanced iPSC model system for the development of novel therapeutic strategies. As an example, the cognitive curves obtained in the longitudinal cohort studies will provide enough variance to assess the effect of epigenetic vulnerability/resilience markers at very early stages of the disease even at pre-dementia stages. Thus, the EPI-AD project will also provide further hints to answer the question on the role of epigenetic markers as maker or markers of the disease. To resolve this question and in order to better diagnose, prevent, attenuate or possibly reverse AD’s pathophysiology, requires moving efforts to earlier disease stages, which is one of the unique assets of the EPI-AD project.