Kristel Sleegers

Summary

Publications

  1. 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
  2. doi request reprint 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
  3. ncbi request reprint 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
  4. doi request reprint 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
  5. ncbi request reprint 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
  6. ncbi request reprint 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
  7. doi request reprint 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
  8. doi request reprint 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
  9. doi request reprint 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
  10. ncbi request reprint 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

Detail Information

Publications39

  1. 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
    ....
  2. doi request reprint 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...
  3. ncbi request reprint 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...
  4. doi request reprint 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...
  5. ncbi request reprint 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)...
  6. ncbi request reprint 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...
  7. doi request reprint 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...
  8. doi request reprint 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...
  9. doi request reprint 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...
  10. ncbi request reprint 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
    ....
  11. doi request reprint 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
    ....
  12. ncbi request reprint 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...
  13. ncbi request reprint 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
    ....
  14. 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...
  15. 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...
  16. doi request reprint 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...
  17. doi request reprint 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...
  18. ncbi request reprint 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...
  19. 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...
  20. ncbi request reprint 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...
  21. ncbi request reprint 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...
  22. ncbi request reprint 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...
  23. 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
    ....
  24. ncbi request reprint 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...
  25. doi request reprint 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...
  26. doi request reprint Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia
    Elise Cuyvers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium Institute Born Bunge, University of Antwerp, Antwerp, Belgium
    Neurobiol Aging 35:726.e11-9. 2014
    ..93×10(-17)). Our data corroborate and extend previous findings to include an increased frequency of rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants may play a role in neurodegenerative diseases in general...
  27. doi request reprint 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...
  28. doi request reprint 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...
  29. pmc Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration
    Julie van der Zee
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Acta Neuropathol 128:397-410. 2014
    ..With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology. ..
  30. ncbi request reprint 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...
  31. doi request reprint 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...
  32. ncbi request reprint Genetic insights in Alzheimer's disease
    Karolien Bettens
    Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium
    Lancet Neurol 12:92-104. 2013
    ..The notional shift needed to make the patient central to genetic studies will necessitate strong collaboration and input from clinical neurologists...
  33. 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...
  34. 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
    ....
  35. doi request reprint Invited article: the Alzheimer disease-frontotemporal lobar degeneration spectrum
    Julie van der Zee
    VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp CDE, Universiteitsplein 1, B 2610, Belgium
    Neurology 71:1191-7. 2008
    ..Herein, we focus on recent exciting findings providing further support for an AD-FTLD spectrum...
  36. doi request reprint Molecular pathogenesis of frontotemporal lobar degeneration: basic science seminar in neurology
    Kristel Sleegers
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Institute for Biotechnology, Flanders, and Laboratory of Neurogenetics, Institute Born Bunge, University of Antwerp, Antwerp, Belgium
    Arch Neurol 65:700-4. 2008
  37. ncbi request reprint 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
    ....
  38. 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...
  39. pmc Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis
    Elke Bogaert
    Laboratory for Neurobiology, Experimental Neurology, University of Leuven, Leuven, Belgium
    Neurobiol Aging 33:418-20. 2012
    ..We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS...