Christine Van Broeckhoven

Summary

Publications

  1. pmc A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats
    Julie van der Zee
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Hum Mutat 34:363-73. 2013
  2. pmc Current status on Alzheimer disease molecular genetics: from past, to present, to future
    Karolien Bettens
    Department of Molecular Genetics, Institute Born Bunge, University of Antwerp, Antwerpen, Belgium
    Hum Mol Genet 19:R4-R11. 2010
  3. pmc TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort
    Julie van der Zee
    Neurodegenerative Brain Disease Group, VIB Department of Molecular Genetics, University of Antwerp CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium
    Brain 134:808-15. 2011
  4. pmc Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 31:763-80. 2010
  5. pmc The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum
    Tim Van Langenhove
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Ann Med 44:817-28. 2012
  6. pmc Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites
    N Brouwers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Mol Psychiatry 17:223-33. 2012
  7. pmc Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice
    Jonathan Janssens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, 2610, Antwerp, Belgium
    Mol Neurobiol 48:22-35. 2013
  8. pmc Mechanisms of granulin deficiency: lessons from cellular and animal models
    Gernot Kleinberger
    Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp CDE, Universiteitsplein 1, Antwerp, 2610, Belgium
    Mol Neurobiol 47:337-60. 2013
  9. doi Distinct clinical characteristics of C9orf72 expansion carriers compared with GRN, MAPT, and nonmutation carriers in a Flanders-Belgian FTLD cohort
    Tim Van Langenhove
    VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp CDE, Universiteitsplein 1, Antwerp, Belgium
    JAMA Neurol 70:365-73. 2013
  10. pmc TMEM106B a novel risk factor for frontotemporal lobar degeneration
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium
    J Mol Neurosci 45:516-21. 2011

Detail Information

Publications95

  1. pmc A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats
    Julie van der Zee
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Hum Mutat 34:363-73. 2013
    ..001) with the most common indel creating one long contiguous imperfect G(4) C(2) repeat, which is likely more prone to replication slippage and pathological expansion...
  2. pmc Current status on Alzheimer disease molecular genetics: from past, to present, to future
    Karolien Bettens
    Department of Molecular Genetics, Institute Born Bunge, University of Antwerp, Antwerpen, Belgium
    Hum Mol Genet 19:R4-R11. 2010
    ....
  3. pmc TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort
    Julie van der Zee
    Neurodegenerative Brain Disease Group, VIB Department of Molecular Genetics, University of Antwerp CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium
    Brain 134:808-15. 2011
    ..Additional studies are needed to unravel the molecular role of TMEM106B in disease onset and pathogenesis...
  4. pmc Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 31:763-80. 2010
    ....
  5. pmc The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum
    Tim Van Langenhove
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Ann Med 44:817-28. 2012
    ..In this review, we review the recent advances that support the existence of an FTLD-ALS spectrum, with particular emphasis on the molecular genetic aspect...
  6. pmc Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites
    N Brouwers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Mol Psychiatry 17:223-33. 2012
    ..How precisely the different functional role of CR1-S in the immune complement cascade contributes to AD pathogenesis will need additional functional studies...
  7. pmc Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice
    Jonathan Janssens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, 2610, Antwerp, Belgium
    Mol Neurobiol 48:22-35. 2013
    ..Furthermore, we show that cellular aggregate formation or accumulation of TDP-43 C-terminal fragments (CTFs) are not primarily responsible for development of the observed disease phenotype in both mutant and wild-type TDP-43 mice...
  8. pmc Mechanisms of granulin deficiency: lessons from cellular and animal models
    Gernot Kleinberger
    Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp CDE, Universiteitsplein 1, Antwerp, 2610, Belgium
    Mol Neurobiol 47:337-60. 2013
    ..Furthermore, we discuss how these insights might help in developing therapeutic strategies for GRN-associated FTD...
  9. doi Distinct clinical characteristics of C9orf72 expansion carriers compared with GRN, MAPT, and nonmutation carriers in a Flanders-Belgian FTLD cohort
    Tim Van Langenhove
    VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp CDE, Universiteitsplein 1, Antwerp, Belgium
    JAMA Neurol 70:365-73. 2013
    ....
  10. pmc TMEM106B a novel risk factor for frontotemporal lobar degeneration
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium
    J Mol Neurosci 45:516-21. 2011
    ..With the TMEM106B gene, a new player has been identified in the pathogenic cascade of FTLD which could hold important implications for the future development of disease-modifying therapies...
  11. doi The future of genetic research on neurodegeneration
    Christine Van Broeckhoven
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Nat Med 16:1215-7. 2010
    ....
  12. ncbi Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    Hum Mutat 30:1054-61. 2009
    ..Furthermore, though mutations is SNCA, PINK1, and PARK7 are rare, our identification of a SNCA duplication confirmed that screening of these genes remains meaningful...
  13. ncbi Alzheimer and Parkinson diagnoses in progranulin null mutation carriers in an extended founder family
    Nathalie Brouwers
    VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp CDE, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
    Arch Neurol 64:1436-46. 2007
    ..Progranulin gene (PGRN) haploinsufficiency was recently associated with ubiquitin-positive frontotemporal lobar degeneration linked to chromosome 17q21 (FTLDU-17)...
  14. ncbi Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population
    Ann Van Den Bogaert
    Applied Molecular Genomics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
    Arch Gen Psychiatry 63:1103-10. 2006
    ..Tryptophan hydroxylase 2 (TPH2) was found to be solely expressed in the brain and therefore considered an important susceptibility gene in psychiatric disorders...
  15. ncbi No association of CSF biomarkers with APOEepsilon4, plaque and tangle burden in definite Alzheimer's disease
    Sebastiaan Engelborghs
    Department of Neurology and Memory Clinic, Middelheim General Hospital ZNA, Antwerpen, Belgium
    Brain 130:2320-6. 2007
    ....
  16. doi Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patients
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Eur J Hum Genet 16:471-9. 2008
    ..Functional data should underlie a conclusion on the pathogenic nature of some mutations that have not been conclusively linked to disease...
  17. doi No association between CALHM1 and risk for Alzheimer dementia in a Belgian population
    Kristel Sleegers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerpen, Belgium
    Hum Mutat 30:E570-4. 2009
    ..Despite its functional properties, our study suggests the polymorphism does not contribute significantly to AD risk in the Belgian population...
  18. doi Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse models
    Sandra Pereson
    Department of Molecular Genetics, VIB, Antwerpen, Belgium
    J Pathol 219:173-81. 2009
    ..Because loss of GRN has recently been shown to cause frontotemporal dementia and serves as a risk factor for AD, the strong GRN reactivity around dense-core plaques is consistent with an important role of this factor in AD pathogenesis...
  19. doi Follow-up study of susceptibility loci for Alzheimer's disease and onset age identified by genome-wide association
    Karolien Bettens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    J Alzheimers Dis 19:1169-75. 2010
    ..90; nominal p = 0.01)). Overall, our data provided independent support for association of at least one chromosomal locus with AD and warranted a more in-depth investigation of these regions for possible underlying functional variants...
  20. ncbi A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Brain 129:841-52. 2006
    ..Together, these results strongly suggest that the DR2-DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations...
  21. doi Cellular ageing, increased mortality and FTLD-TDP-associated neuropathology in progranulin knockout mice
    Hans Wils
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    J Pathol 228:67-76. 2012
    ..Our data suggest that progranulin deficiency in mice leads to reduced survival in adulthood and increased cellular ageing accompanied by hyperphosphorylation of TDP-43, and recapitulates key aspects of FTLD-TDP neuropathology...
  22. ncbi Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
    Marc Cruts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
    Nature 442:920-4. 2006
    ..Furthermore, in a Belgian series of familial FTD patients, PGRN mutations were 3.5 times more frequent than mutations in MAPT, underscoring a principal involvement of PGRN in FTD pathogenesis...
  23. ncbi Characterization of ubiquitinated intraneuronal inclusions in a novel Belgian frontotemporal lobar degeneration family
    Daniel Pirici
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB8, Institute Born Bunge, University of Antwerp, Belgium
    J Neuropathol Exp Neurol 65:289-301. 2006
    ..Whereas the precise nature of the protein remains elusive, characterization of such familial FTLD-U patients would be helpful in identifying a common denominator in the pathogenesis of familial and the more prevalent sporadic FTLD-U...
  24. ncbi Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in recurrent major depressive disorder
    Filip Van Den Eede
    Department of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Psychiatry Res 153:17-25. 2007
    ..The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample...
  25. ncbi Intraneuronal amyloid beta and reduced brain volume in a novel APP T714I mouse model for Alzheimer's disease
    Bianca Van Broeck
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
    Neurobiol Aging 29:241-52. 2008
    ..These data support earlier observations of A beta accumulation in the endosomal-lysosomal pathway and the hypothesis that intraneuronal accumulation of A beta could be an important factor in the AD pathogenesis...
  26. doi Contribution of TARDBP to Alzheimer's disease genetic etiology
    Nathalie Brouwers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    J Alzheimers Dis 21:423-30. 2010
    ..In conclusion, the genetic contribution of TARDBP to AD was restricted to the rare mutation p.Ala90Val (3/739, 0.4%) of unclear pathogenic nature that affects the nuclear localization signal in TDP-43...
  27. doi Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease
    Veerle Bogaerts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 29:832-40. 2008
    ..The latter underpins a previously unrecognized role for altered HTRA2 expression as a risk factor relevant to parkinsonian neurodegeneration...
  28. doi Reduced brain volumes in mice expressing APP-Austrian mutation but not in mice expressing APP-Swedish-Austrian mutations
    Bianca Van Broeck
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Neurosci Lett 447:143-7. 2008
    ..These data also provide a first in vivo indication of altered processing of APP-Swedish at sub-endogenous levels, an effect not observed in mouse models expressing the APP-Swedish mutation in high amounts...
  29. doi Comprehensive genetic and mutation analysis of familial dementia with Lewy bodies linked to 2q35-q36
    Bram Meeus
    Department of Molecular Genetics, VIB, Antwerpen, Belgium
    J Alzheimers Dis 20:197-205. 2010
    ..Nevertheless, identifying the first familial DLB gene is likely to contribute an entry point into the pathogenic cascades underlying DLB pathology...
  30. doi Identification of 2 Loci at chromosomes 9 and 14 in a multiplex family with frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Ilse Gijselinck
    University of Antwerp, B 2610 Antwerp, Belgium
    Arch Neurol 67:606-16. 2010
    ..Frontotemporal lobar degeneration (FTLD) is a neurodegenerative brain disorder that can be accompanied by signs of amyotrophic lateral sclerosis (ALS)...
  31. ncbi DNMBP is genetically associated with Alzheimer dementia in the Belgian population
    Karolien Bettens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium
    Neurobiol Aging 30:2000-9. 2009
    ..Taken together our findings underscore a role for DNMBP in the genetic risk for late-onset AD in the Belgian population...
  32. pmc TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration
    Hans Wils
    Department of Molecular Genetics, VIB, B 2610 Antwerpen, Belgium
    Proc Natl Acad Sci U S A 107:3858-63. 2010
    ..These findings suggest that approximately 25-kDa TDP-43 CTFs are noxious to neurons by a gain of aberrant nuclear function...
  33. ncbi Cerebrospinal fluid Aβ1-40 improves differential dementia diagnosis in patients with intermediate P-tau181P levels
    Sylvie Slaets
    Reference Center for Biological Markers of Dementia, Laboratory of Neurochemistry and Behavior, Institute Born Bunge, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium
    J Alzheimers Dis 36:759-67. 2013
    ....
  34. ncbi Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS
    Ilse Gijselinck
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Belgium
    Neurobiol Aging 30:1329-31. 2009
    ..Our data implicate that TDP-43 has no primary genetic role in the pathophysiological mechanisms underlying central nervous system neurodegeneration in these diseases...
  35. ncbi Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40
    Samir Kumar-Singh
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology, University of Antwerp, Antwerpen, Belgium
    Hum Mutat 27:686-95. 2006
    ..Also, the in vitro method we describe here is a valid tool for assaying the pathogenic potential of clinical PSEN mutations in a molecular diagnostic setting...
  36. ncbi CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mol Genet 17:313-22. 2008
    ..We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive...
  37. ncbi Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in bipolar disorder
    Filip Van Den Eede
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium
    Psychiatr Genet 17:304-7. 2007
    ..In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder...
  38. ncbi Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's disease
    Nathalie Brouwers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics Flanders Interuniversity Institute for Biotechnology Antwerpen, Belgium
    Brain 129:2984-91. 2006
    ....
  39. doi A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study
    Ilse Gijselinck
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Lancet Neurol 11:54-65. 2012
    ..A locus on chromosome 9p21 has been associated with both disorders, and we aimed to identify the causal gene within this region...
  40. doi DLB and PDD: a role for mutations in dementia and Parkinson disease genes?
    Bram Meeus
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Neurobiol Aging 33:629.e5-629.e18. 2012
    ..They do support the hypothesis of a genetic overlap between members of the Lewy body disease spectrum, but additional genes still have to exist...
  41. doi Common variation in GRB-associated Binding Protein 2 (GAB2) and increased risk for Alzheimer dementia
    Kristel Sleegers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp CDE, Universiteitsplein 1, B 2610 Antwerpen, Belgium
    Hum Mutat 30:E338-44. 2009
    ..6). The association was driven by a higher frequency of the major haplotype in patients. Our data independently replicate an association between GAB2 and late-onset AD, which appears to be limited to APOE epsilon4 carriers...
  42. doi Complement receptor 1 coding variant p.Ser1610Thr in Alzheimer's disease and related endophenotypes
    Caroline Van Cauwenberghe
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Neurobiol Aging 34:2235.e1-6. 2013
    ....
  43. doi SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population
    Karolien Bettens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerpen, Belgium
    Hum Mutat 29:769-70. 2008
    ..Our findings confirm that genetic variants in SORL1 may be important risk factors for late-onset AD...
  44. ncbi The UBQLN1 polymorphism, UBQ-8i, at 9q22 is not associated with Alzheimer's disease with onset before 70 years
    Nathalie Brouwers
    Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology and Institute Born Bunge, University of Antwerp, Universiteitsplein 1, Belgium
    Neurosci Lett 392:72-4. 2006
    ..Our study does not support a major role for this UBQLN1 polymorphism in AD patients with an earlier onset of disease...
  45. ncbi High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy
    Rosa Rademakers
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
    Hum Mol Genet 14:3281-92. 2005
    ..Thus, risk variants on different H1 htSNP haplotypes and protective variants on H2 contribute to population risk for PSP...
  46. pmc Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample
    Rosa Rademakers
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 77:643-52. 2005
    ....
  47. doi Longitudinal stability of cerebrospinal fluid biomarker levels: fulfilled requirement for pharmacodynamic markers in Alzheimer's disease
    Nathalie Le Bastard
    Laboratory of Neurochemistry and Behavior, Reference Center for Biological Markers of Dementia BIODEM, Antwerp, Belgium
    J Alzheimers Dis 33:807-22. 2013
    ..Only T-tau increased in AD patients in comparison to controls, which does not preclude its use as a diagnostic marker, nor as a potential pharmacodynamic marker...
  48. doi Serum biomarker for progranulin-associated frontotemporal lobar degeneration
    Kristel Sleegers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB Flanders Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium
    Ann Neurol 65:603-9. 2009
    ..Mutations that lead to a loss of progranulin (PGRN) explain a considerable portion of the occurrence of frontotemporal lobar degeneration. We tested a biomarker allowing rapid detection of a loss of PGRN...
  49. ncbi Genomic architecture of human 17q21 linked to frontotemporal dementia uncovers a highly homologous family of low-copy repeats in the tau region
    Marc Cruts
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Hum Mol Genet 14:1753-62. 2005
    ..The presence of multiple homologous LCRs in the region predicts that other potentially more complex genomic rearrangements might be underlying FTDU-17...
  50. doi C9orf72 G4C2 repeat expansions in Alzheimer's disease and mild cognitive impairment
    Rita Cacace
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Neurobiol Aging 34:1712.e1-7. 2013
    ..Non-pathogenic repeat length variability did not affect risk of AD or MCI, nor AD biomarker levels in CSF, indicating that C9orf72 is not a direct AD risk factor...
  51. pmc Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer disease
    Jessie Theuns
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, University of Antwerp, Antwerpen, Belgium
    Am J Hum Genet 78:936-46. 2006
    ..The present study provides evidence that APP-promoter mutations that significantly increase APP expression levels are associated with AD...
  52. ncbi Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 28:416. 2007
    ..Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD...
  53. ncbi A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder
    Veerle Bogaerts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Institute Born Bunge, Antwerpen, Belgium
    Brain 130:2277-91. 2007
    ..Once identified this will be the first novel causal gene for DLB and can be expected to open new avenues for biological studies of the disease process...
  54. doi Contribution of VPS35 genetic variability to LBD in the Flanders-Belgian population
    Aline Verstraeten
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    Neurobiol Aging 33:1844.e11-3. 2012
    ..Hence, our data do not support a major role for VPS35 variations in the genetic etiology of Lewy body disorders in the Flanders-Belgian population...
  55. doi Ataxin-2 polyQ expansions in FTLD-ALS spectrum disorders in Flanders-Belgian cohorts
    Tim Van Langenhove
    Department of Molecular Genetics, VIB, Universiteitsplein 1, Antwerpen, Belgium
    Neurobiol Aging 33:1004.e17-20. 2012
    ..Our results provide further support to the notion that ATXN2 associated polyglutamine amplification is specific to the ALS-end of the FTLD-ALS disease spectrum...
  56. pmc Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk
    Karolien Bettens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, 2610 Antwerpen, Belgium
    Mol Neurodegener 7:3. 2012
    ....
  57. doi GIGYF2 has no major role in Parkinson genetic etiology in a Belgian population
    Bram Meeus
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, B 2610 Antwerpen, Belgium
    Neurobiol Aging 32:308-12. 2011
    ..Together, our results do not support a role for GIGYF2 in the genetic etiology of Belgian PD...
  58. pmc The gene encoding nicastrin, a major gamma-secretase component, modifies risk for familial early-onset Alzheimer disease in a Dutch population-based sample
    Bart Dermaut
    Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, B 2610 Antwerpen, Belgium
    Am J Hum Genet 70:1568-74. 2002
    ..1; 95% confidence interval 1.2-13.3; P=.01). These results are compatible with an important role of gamma-secretase dysfunction in the etiology of familial EOAD...
  59. ncbi Tau is central in the genetic Alzheimer-frontotemporal dementia spectrum
    Bart Dermaut
    Department of Molecular Genetics VIB 8, Flanders Interuniversity Institute for Biotechnology, Neurodegenerative Brain Diseases Group, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B 2610 Antwerpen, Belgium
    Trends Genet 21:664-72. 2005
    ..Together, these studies suggest that AD and FTD are linked in a genetic spectrum of presenile degenerative brain disorders in which tau appears to be the central player...
  60. ncbi Amyloid pathology influences aβ1-42 cerebrospinal fluid levels in dementia with lewy bodies
    Sylvie Slaets
    Reference Center for Biological Markers of Dementia BIODEM, Laboratory of Neurochemistry and Behavior, Institute Born Bunge, University of Antwerp, Antwerp, Belgium
    J Alzheimers Dis 35:137-46. 2013
    ....
  61. pmc novoSNP, a novel computational tool for sequence variation discovery
    Stefan Weckx
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Genome Res 15:436-42. 2005
    ....
  62. doi Increased caspase activation and decreased TDP-43 solubility in progranulin knockout cortical cultures
    Gernot Kleinberger
    Department of Molecular Genetics, VIB, Universiteitsplein 1, Antwerpen, Belgium
    J Neurochem 115:735-47. 2010
    ..This leads to increased aggregation and accumulation of full-length TDP-43 along with its C-terminal derivatives by both caspase-dependent and independent mechanisms...
  63. ncbi Genetic variant in the HSPB1 promoter region impairs the HSP27 stress response
    Ines Dierick
    Peripheral Neuropathy Group, University of Antwerp, Universiteitsplein 1, Antwerpen, Belgium
    Hum Mutat 28:830. 2007
    ..Therefore, our study suggests that the functional HSPB1 variant may represent a genetic modifier in the pathogenesis of motor neuron disease; however, it is necessary to confirm this HSPB1 variant in additional ALS patients...
  64. doi Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia
    Jessie Theuns
    Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium
    Mov Disord 27:1451-6. 2012
    ..Autosomal dominant dopa-responsive dystonia (AD-DRD) is caused by a biochemical defect primarily resulting from guanosine triphosphate cyclohydrolase 1 gene (GCH1) mutations. Few families have been reported without mutations in GCH1...
  65. pmc The genetics and neuropathology of frontotemporal lobar degeneration
    Anne Sieben
    Institute Born Bunge, University of Antwerp, Antwerpen, Belgium
    Acta Neuropathol 124:353-72. 2012
    ..In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition...
  66. ncbi SNPbox: a modular software package for large-scale primer design
    Stefan Weckx
    Department of Molecular Genetics, Bioinformatics Unit, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, B 2610 Antwerpen, Belgium
    Bioinformatics 21:385-7. 2005
    ..Of the 2500 primer sets designed by SNPbox, 95% successfully amplified genomic DNA under uniform PCR conditions...
  67. ncbi Frontotemporal lobar degeneration with ubiquitin-positive inclusions: a molecular genetic update
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Laboratory of Neurogenetics, Institute Born Bunge, and University of Antwerp, Antwerp, Belgium
    Neurodegener Dis 4:227-35. 2007
    ..This review focuses on the molecular genetic processes underlying FTLD-U pathology...
  68. ncbi Brain-specific tryptophan hydroxylase, TPH2, and 5-HTTLPR are associated with frontal lobe symptoms in Alzheimer's disease
    Sebastiaan Engelborghs
    Department of Neurology and Memory Clinic, Middelheim and Hoge Beuken General Hospitals ZNA, Antwerpen, Belgium
    J Alzheimers Dis 35:67-73. 2013
    ....
  69. ncbi A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques
    Bart Dermaut
    Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology VIB8, University of Antwerp, Antwerpen, Belgium
    Ann Neurol 55:617-26. 2004
    ..Our results suggest PS1 as a candidate gene for Pick-type tauopathy without MAPT mutations...
  70. ncbi No allelic association or interaction of three known functional polymorphisms with bipolar disorder in a northern Swedish isolated population
    Ann Van Den Bogaert
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium
    Psychiatr Genet 16:209-12. 2006
    ....
  71. pmc Genomewide scan for affective disorder susceptibility Loci in families of a northern Swedish isolated population
    Tine Venken
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 76:237-48. 2005
    ..These results suggest a susceptibility locus on 9q31-q33 for affective disorder in this common ancestral region...
  72. ncbi APP and BACE1 miRNA genetic variability has no major role in risk for Alzheimer disease
    Karolien Bettens
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    Hum Mutat 30:1207-13. 2009
    ..033). While the exact role of the patient-specific miRNA variants within the 3' UTR region of APP and BACE1 demands further analyses, this study does not support a major contribution of miRNA genetic variability to AD pathogenesis...
  73. ncbi Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression
    Dirk van West
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp, Antwerp, Belgium
    Neuropsychopharmacology 31:620-7. 2006
    ..This study suggests that polymorphisms in the 5' region of the NR3C1 gene may play a role in the genetic vulnerability for MDD...
  74. pmc Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls
    Samir Kumar-Singh
    Department of Molecular Genetics VIB8, Neurodegenerative Brain Diseases Research Group, Molecular Neuropathology Project, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Am J Pathol 167:527-43. 2005
    ....
  75. ncbi Alzheimer-associated C allele of the promoter polymorphism -22C>T causes a critical neuron-specific decrease of presenilin 1 expression
    Jessie Theuns
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Hum Mol Genet 12:869-77. 2003
    ..Together, these studies provide evidence that the increased risk for AD associated with PSEN1 may result from genetic variations in the regulatory region, leading to altered expression levels of PSEN1 in neurons...
  76. ncbi Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches
    Bianca Van Broeck
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein I, BE 2610 Antwerp, Belgium
    Neurodegener Dis 4:349-65. 2007
    ..Secondly, considering these mechanistic insights, we will discuss some therapeutic strategies which are currently in clinical or preclinical trials for AD...
  77. ncbi SNPbox: web-based high-throughput primer design with an eye for repetitive sequences
    Stefan Weckx
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp, Belgium
    Methods Mol Biol 402:179-200. 2007
    ..SNPbox.org, and explain how pre-designed primers for Ensembl genes can be visualized and retrieved...
  78. doi Microglial upregulation of progranulin as a marker of motor neuron degeneration
    Thomas Philips
    Vesalius Research Center, VIB, Leuven, Belgium
    J Neuropathol Exp Neurol 69:1191-200. 2010
    ..These data indicate that upregulation of PGRN is a marker of the microglial response that occurs with progression in motor neuron diseases...
  79. pmc SNPbox: web-based high-throughput primer design from gene to genome
    Stefan Weckx
    Department of Molecular Genetics, Bioinformatics Unit, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
    Nucleic Acids Res 32:W170-2. 2004
    ..The data of this genome-wide SNPbox application can be visualized in Ensembl's ContigView through a DAS (distributed annotation system) annotation server...
  80. ncbi Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementia
    Sebastiaan Engelborghs
    Department of Neurology and Memory Clinic, Middelheim General Hospital, ZNA, Antwerp, Belgium
    Neurobiol Aging 27:285-92. 2006
    ..In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB)...
  81. doi Molecular genetics of Alzheimer's disease: an update
    Nathalie Brouwers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Ann Med 40:562-83. 2008
    ..This review provides an overview of the current understanding in the field of AD genetics, covering both the rare monogenic forms as well as recent developments in the search for novel AD susceptibility genes...
  82. doi Molecular pathways of frontotemporal lobar degeneration
    Kristel Sleegers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, B 2610 Antwerpen, Belgium
    Annu Rev Neurosci 33:71-88. 2010
    ..g., the role of FUS in amyotrophic lateral sclerosis...
  83. doi Associations between common arginine vasopressin 1b receptor and glucocorticoid receptor gene variants and HPA axis responses to psychosocial stress in a child psychiatric population
    Dirk van West
    Department of Molecular Genetics, Applied Molecular Genomics Group, VIB, Belgium
    Psychiatry Res 179:64-8. 2010
    ..However, the small number of ER22/23EK subjects does not allow us to draw definitive conclusions about the genotypic effect...
  84. ncbi Genetics and pathology of alpha-secretase site AbetaPP mutations in the understanding of Alzheimer's disease
    Christine Van Broeckhoven
    Department of Molecular Genetics, Neurodegenerative Brain Diseases Research Group, Flanders Interuniversity Institute for Biotechnology, Institute Born Bunge and University of Antwerp, Antwerpen, Belgium
    J Alzheimers Dis 9:389-98. 2006
    ..In addition, this review will also point directions that warrant additional studies...
  85. pmc Locus-specific mutation databases for neurodegenerative brain diseases
    Marc Cruts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 33:1340-4. 2012
    ..Finally, with the exception of the PD genes PARK2 and PINK1, all other genes are associated with more than one clinical diagnosis or characteristics thereof...
  86. ncbi Progranulin mutations in ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
    Marc Cruts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    Curr Alzheimer Res 3:485-91. 2006
    ..These findings open promising novel targets for therapeutic intervention against neurodegeneration...
  87. ncbi PRNP Val129 homozygosity increases risk for early-onset Alzheimer's disease
    Bart Dermaut
    Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology VIB8, University of Antwerp, Antwerpen, Belgium
    Ann Neurol 53:409-12. 2003
    ..2; 95% CI, 1.4-7.1; p < 0.01). In patients with a positive family history, these risks increased to 2.6 (95% CI, 1.3-5.3; p < 0.01) and 3.5 (95% CI, 1.3-9.3; p = 0.01), respectively...
  88. doi Loss of progranulin function in frontotemporal lobar degeneration
    Marc Cruts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    Trends Genet 24:186-94. 2008
    ..The high variability in onset age and age-dependent penetrance suggests that the PGRN pathway is highly susceptible to modulating factors that might be exploited to delay the disease processes...
  89. ncbi The corticotropin-releasing hormone binding protein is associated with major depression in a population from Northern Sweden
    Stephan Claes
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Belgium
    Biol Psychiatry 54:867-72. 2003
    ..Therefore, the gene encoding for corticotropin releasing hormone binding protein is a functional candidate gene for major depression...
  90. doi The pursuit of susceptibility genes for Alzheimer's disease: progress and prospects
    Kristel Sleegers
    Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics Universiteitsplein 1, B 2610 Antwerp, Belgium
    Trends Genet 26:84-93. 2010
    ..We discuss how these and future findings can be translated into efforts to ameliorate patient care by genetic profiling for risk prediction and pharmacogenetics and by guiding drug development...
  91. pmc Amyloid precursor protein mutation E682K at the alternative β-secretase cleavage β'-site increases Aβ generation
    Lujia Zhou
    Department for Developmental and Molecular Genetics, VIB, Leuven, Belgium
    EMBO Mol Med 3:291-302. 2011
    ..We propose to classify the E682K mutation as probable pathogenic awaiting further independent confirmation of its association with AD in other patients...
  92. ncbi De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy
    Lieve Claes
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, Born Bunge Foundation, University of Antwerp UIA, Antwerpen, Belgium
    Hum Mutat 21:615-21. 2003
    ..In contrast to our previous study, most mutations are missense mutations clustering in the S4-S6 region of SCN1A. These findings demonstrate that de novo mutations in SCN1A are a major cause of isolated SMEI...
  93. ncbi Major affective disorders and schizophrenia: a common molecular signature?
    Ann Van Den Bogaert
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Hum Mutat 27:833-53. 2006
    ..Also, we discuss the current knowledge and hypotheses that have been formulated regarding the effect of variations on protein functioning as well as recent observations that point to common molecular mechanisms...
  94. ncbi European combined analysis of the CTG18.1 and the ERDA1 CAG/CTG repeats in bipolar disorder
    Jurgen Del-Favero
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp UIA, Belgium
    Eur J Hum Genet 10:276-80. 2002
    ..We conclude that the ERDA-1 locus is not related to the BP phenotype while expanded alleles at the CTG18.1 locus cannot be excluded as a vulnerability factor for BP disorder...