Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease

R. Rademakers, K. Sleegers, J. Theuns, M. Van Den Broeck, S. Bel Kacem, L. G. Nilsson, R. Adolfsson, C. M. Van Duijn, C. Van Broeckhoven, M. Cruts

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Malfunctioning of cyclin-dependent kinase 5 (CDK5) through aberrant proteolytic cleavage of its neuronal activators p35 and p39 is involved in neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative brain diseases. By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients. We performed an association study with five informative SNPs in CDK5 in two independent samples of early-onset AD patients and matched control individuals from The Netherlands and northern Sweden. Association was observed with g.149800G>C in intron 5 of CDK5, and a two times increased risk was observed in both patient samples for carriers of the C-allele. Our data are indicative for a role of the CDK5 molecular complex in the genetic etiology of early-onset AD, and suggest that a yet unknown functional variant in CDK5 or in a nearby gene might lead to increased susceptibility for early-onset AD.

Original languageEnglish (US)
Pages (from-to)1145-1151
Number of pages7
JournalNeurobiology of aging
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2005

Keywords

  • Alzheimer dementia
  • Association analysis
  • Cyclin-dependent kinase
  • Mutation analysis
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Rademakers, R., Sleegers, K., Theuns, J., Van Den Broeck, M., Bel Kacem, S., Nilsson, L. G., Adolfsson, R., Van Duijn, C. M., Van Broeckhoven, C., & Cruts, M. (2005). Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease. Neurobiology of aging, 26(8), 1145-1151. https://doi.org/10.1016/j.neurobiolaging.2004.10.003