Christine Van Broeckhoven
Neurodegenerative Brain Diseases
VIB Department of Molecular Genetics, University of Antwerp

PhD: Univ. of Antwerp, Antwerp, Belgium, '80 DSc Molecular Genetics: Univ. of Antwerp, Antwerp, Belgium, '94 VIB Group leader since 1996 Scientific Director, Dept. of Molecular Genetics since 1996 Professor Univ.of Antwerp since 1997

e-mail phone +32 3 265 10 02 ADDRESS

Current team members
Group leader: Christine Van Broeckhoven
Project leaders: Marc Cruts, Samir Kumar-Singh
Staff scientists: Jessie Theuns, Kristel Sleegers
Postdoctoral scientists: Ilse Gijselinck, Julie van der Zee, Karen Nuytemans, Nathalie Brouwers
Ph.D. Students: Bram Meeus, Caroline Van Cauwenberghe, David Crosiers, Gernot Kleinberger, Hans Wils, Jonathan Janssens, Karolien Bettens, Sandra Pereson, Tim Van Langenhove
Support personnel: Ana Gil Montoya, Ellen Corsmit, Ellen Elinck, Geert Joris, Githa Maes, Helen Van Miegroet, Ivy Cuijt, Jamila Ben Azza, Jolien Brys, Karin Peeters, Maria Mattheijssens, Marleen Van den Broeck, Veerle Bäumer

Keywords
Alzheimer’s disease - frontotemporal dementia - Parkinson's disease - genetics - genomics - neuropathology - mouse transgenesis

Science

Our focus is on genetics, genomics and neuropathology of the neurodegenerative brain diseases Alzheimer’s disease (AD), frontal temporal lobar degeneration (FTLD) and Parkinson’s disease (PD), attempting to find molecular mechanisms of protein aggregation in dementia. We systematical collect large samples of patients and relatives for genetic studies aiming at identifying disease genes using either a positional cloning strategy in multiplex families or association studies in patient/control groups. Novel key proteins that are potential drug targets for more effective treatment are analyzed in cellular and mouse models.
Using this integrated approach we have already made several major contributions to AD with the identification of the Flemish and Austrian mutations in the amyloid precursor protein gene (APP) that have highlighted the relationship between neuronal and vascular components of AD pathology as well as of different Aβ plaque deposits. We also showed that select mutations in presenilin 1 (PS1) and APP are actually causing a significant decrease of Aβ40 production suggesting a loss of function mechanism in AD. And we identified in APP mutations in the 5’ regulatory region that increase APP expression to levels comparable to that observed in Down syndrome patients. More recently we identified progranulin (PGRN) as a second common gene for FTLD in which dominant loss-of-function mutations cause neurodegeneration. We also demonstrated genetic and clinical heterogeneity with PGRN contributing to FTLD, AD, PD as well as amyotrophic lateral sclerosis (ALS).
In our current research we aim at further unraveling genetic heterogeneity by identifying novel chromosomal loci and by mapping the underlying genes for AD at 7q36 and for dementia with Lewy bodies at 2q35-q36 that we recently reported. Also, we will continue our efforts at identifying the genetic modifying factor that contributes to the highly variable onset ages in PGRN mutation carriers. The extended patient and control groups will be used for genetic association studies to unravel spectrum of genetic factors that contribute to risk for these diseases. In these groups, we are investing in the collection of biosamples for proteomics and QTL mapping of endophenotypic disease markers. To elucidate the mechanism of neurodegeneration due to loss-of-function mutations in PGRN, we generated knockout and overexpressing PGRN mice. Comparable experiments will be done in cellular models. Our efforts in understanding the mechanisms of Aβ plaque formation using transgenic mouse models will be broadened to the identification of key proteins that are involved in the Aβ aggregation.

Press Releases
See also press release (06/03/2009): Blood test predicts chance of dementia - based on the publication in Annals of Neurology (Sleegers et al., Annals of Neurology, 2009)

See also press release (02/02/2009): Christine Van Broeckhoven to be knighted.

See also press release (18/12/2008): Alzheimer’s disease yesterday, today and tomorrow.

Sleegers K, Brouwers N, Van Damme P, Engelborghs S, Gijselinck I, van der Zee J, Peeters K, Mattheijssens M, Cruts M, Vandenberghe R, De Deyn P, Robberecht W, Van Broeckhoven C
Serum biomarker for progranulin-associated frontotemporal lobar degeneration
ANN NEUROL 65, 603-9, 2009



Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere M, Pahwa J, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan A, Lovestone S, Powell J, Proitsi P, Lupton M, Brayne C, Rubinsztein D, Gill M, Lawlor B, Lynch A, Morgan K, Brown K, Passmore P, Craig D, Mcguinness B, Todd S, Holmes C, Mann D, Smith A, Love S, Kehoe P, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schurmann B, Van Den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Hull M, Rujescu D, Goate A, Kauwe J, Cruchaga C, Nowotny P, Morris J, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn P, Van Broeckhoven C, Livingston G, Bass N, Gurling H, Mcquillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw C, Tsolaki M, Singleton A, Guerreiro R, Muhleisen T, Nothen M, Moebus S, Jockel K, Klopp N, Wichmann H, Carrasquillo M, Pankratz V, Younkin S, Holmans P, O'donovan M, Owen M, Williams J
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
NAT GENET 41, 1088-93, 2009



Lambert J, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido M, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fievet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, De Pancorbo M, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossu P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F, Soininen H, Ritchie K, Blanche H, Dartigues J, Tzourio C, Gut I, Van Broeckhoven C, Alperovitch A, Lathrop M, Amouyel P
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
NAT GENET 41, 1094-9, 2009



Cruts M, Van Broeckhoven C
Loss of progranulin function in frontotemporal lobar degeneration
TRENDS GENET 24, 186-94, 2008



Theuns J, Brouwers N, Engelborghs S, Sleegers K, Bogaerts V, Corsmit E, De Pooter T, van Duijn C, De Deyn P, Van Broeckhoven C
Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer disease
AM J HUM GENET 78, 936-46, 2006



Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin J, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn P, Kumar-Singh S, Van Broeckhoven C
Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
NATURE 442, 920-4, 2006

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