The focus of our research team is on translational neurogenetics of frontotemporal dementia (FTD) and early onset dementia. Hereto, we apply advanced genomic sequencing approaches on well- characterized patient collections and biomaterials collected through the coordination of national and international neurology networks. Although dementia is generally considered an aging disease affecting the elderly, in about one in ten patients, dementia symptoms present before the age of 65 years, referred to as early-onset dementia (EOD). Together with Alzheimer’s disease (AD), FTD is one of the primary causes of EOD. Reflected by their early disease presentation, EOD patients often have a high genetic burden and often present with Mendelian familial inheritance. This makes these EOD patients and families particularly powerful for gene identification studies, which may pinpoint novel molecular pathways and targets for therapy devolvement with relevance to a larger cohort of dementia patients (not just limited to early onset dementia).
In 2011, Julie van der Zee and Christine Van Broeckhoven founded and coordinate the European Early-Onset Dementia (EU EOD) Consortium, bringing together 41 expert research groups across Europe, joining efforts to collect well-documented patient cohorts of rare and understudied early-onset forms of dementia for neurogenetic and clinical research. This multidisciplinary collaboration has led to a unique collection of EOD study populations with long clinical follow-up and patient biomaterials. The aim of the EU EOD Consortium is to promote gene-discovery and do first-line epidemiological characterization of novel dementia genes in terms of mutation spectrum,
frequency and genotype-phenotype correlations. As such, we cover the whole realm of translational genetic dementia research, starting at the collection of powerful, well-documented patient cohorts, promoting gene-discovery, to epidemiological characterization of novel dementia genes, investigation of different mutation/disease mechanisms and translation into diagnostic and prognostic relevant genotype-phenotype correlations.
Ongoing projects include exome and genome sequencing-based gene hunting in FTD and other EODs in families and patient cohorts. We apply advanced genomic and computational biological pathway-based approaches for rare-variant prioritization in search of novel disease-causing or -modifying genes. In addition to our gene-discovery research lines, in close collaboration with our partners in the clinic, we invest in the multimodal molecular profiling of dementia patients based on clinical, genetic, biochemical, imaging and electrophysiological markers. Through this synergy of expertise, we aim to develop multimodal markers to address the early preclinical development, and molecular complexity of dementia phenotypes like AD and FTD, for improved early and differential dementia diagnosis based on the molecular profile of the patient. In addition to improved differential diagnosis, this will allow to define optimal target populations for precision medicine-based therapeutic intervention trials.
- van der Zee J Gijselinck I, Van Mossevelde S, Perrone F, Dillen L, Heeman B, Bäumer V, Engelborghs S, De Bleecker J, Baets J, Gelpi E, Rojas-García R, Clarimón J, Lleó A, Diehl-Schmid J, Alexopoulos P, Perneczky R, Synofzik M, Just J, Schöls L, Graff C, Thonberg H, Borroni B, Padovani A, Jordanova A, Sarafov S, Tournev I, de Mendonça A, Miltenberger-Miltényi G, Simões do Couto F, Ramirez A, Jessen F, Heneka MT, Gómez-Tortosa E, Danek A, Cras P, Vandenberghe R, De Jonghe P, De Deyn PP, Sleegers K, Cruts M, Van Broeckhoven C, Belgian Neurology Consortium and European Early-Onset Dementia Consortium: TBK1 mutation spectrum in an extended European patient cohort with frontotemporal dementia and amyotrophic lateral sclerosis. Human Mutation 2017; 38(3):297-309
- van der Zee J Van Langenhove T, Kovacs GG, Dillen L, Deschamps W, Engelborghs S, Matěj R, Vandenbulcke M, Sieben A, Dermaut B, Smets K, Van Damme P, Merlin C, Laureys A, Van Den Broeck M, Mattheijssens M, Peeters K, Benussi L, Binetti G, Ghidoni R, Borroni B, Padovani A, Archetti S, Pastor P, Razquin C, Ortega-Cubero S, Hernández I, Boada M, Ruiz A, de Mendonça A, Miltenberger-Miltényi G, do Couto FS, Sorbi S, Nacmias B, Bagnoli S, Graff C, Chiang HH, Thonberg H, Perneczky R, Diehl-Schmid J, Alexopoulos P, Frisoni GB, Bonvicini C, Synofzik M, Maetzler W, vom Hagen JM, Schöls L, Haack TB, Strom TM, Prokisch H, Dols-Icardo O, Clarimón J, Lleó A, Santana I, Almeida MR, Santiago B, Heneka MT, Jessen F, Ramirez A, Sanchez-Valle R, Llado A, Gelpi E, Sarafov S, Tournev I, Jordanova A, Parobkova E, Fabrizi GM, Testi S, Salmon E, Ströbel T, Santens P, Robberecht W, De Jonghe P, Martin JJ, Cras P, Vandenberghe R, De Deyn PP, Cruts M, Sleegers K, Van Broeckhoven C, BELNEU Consortium, EU EOD Consortium: Rare mutations in SQSTM1 modify susceptibility for frontotemporal lobar degeneration. Acta Neuropathologica 2014; 128: 397-410
- van der Zee J Van Broeckhoven C: Dementia in 2013: Frontotemporal lobar degeneration - building on breakthroughs. Nature Reviews Neurology 2014; 10(2): 70-72
- van der Zee J Gijselinck I, Dillen L, Van Langenhove T, Theuns J, Engelborghs S, Philtjens S, Vandenbulcke M, Sleegers K, Sieben A, Bäumer V, Maes G, Corsmit E, Borroni B, Padovani A, Archetti S, Perneczky R, Diehl-Schmid J, de Mendonça A, Miltenberger-Miltenyi G, Pereira S, Pimentel J, Nacmias B, Bagnoli S, Sorbi S, Graff C, Chiang HH, Westerlund M, Sanchez-Valle R, Llado A, Gelpi E, Santana I, Almeida MR, Santiago B, Frisoni G, Zanetti O, Bonvicini C, Synofzik M, Maetzler W, Vom Hagen JM, Schöls L, Heneka MT, Jessen F, Matej R, Parobkova E, Kovacs GG, Ströbel T, Sarafov S, Tournev I, Jordanova A, Danek A, Arzberger T, Fabrizi GM, Testi S, Salmon E, Santens P, Martin JJ, Cras P, Vandenberghe R, De Deyn PP, Cruts M, Van Broeckhoven C, on behalf of the European Early-Onset Dementia Consortium: A Pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability and intermediate repeats. Human Mutation 2013; 34(2): 363-373
- Cruts M, Gijselinck I, van der Zee J Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, Van Broeckhoven C.: Null mutations in progranulin cause ubiquitine-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442: 920-924