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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 publication

DOI

10.1016/j.neurobiolaging.2004.10.003

Type

Journal article

Journal

Neurobiol Aging

Publication Date

08/2005

Volume

26

Pages

1145 - 1151

Keywords

Aged, Alzheimer Disease, Cyclin-Dependent Kinase 5, Cyclin-Dependent Kinases, DNA Mutational Analysis, Exons, Female, Gene Frequency, Genetic Testing, Genetic Variation, Genotype, Haplotypes, Humans, Introns, Male, Middle Aged, Mutation, Nerve Tissue Proteins, Netherlands, Sweden