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http://purl.uniprot.org/citations/19154537http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19154537http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Glycogen synthase kinase-3beta (GSK-3beta) and cyclin-dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1) encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and GSK-3beta genes are related to phosphorylation of tau, we examined the combined contribution of these genes to the susceptibility for AD.

Methods

In a case-control study in 283 AD patients and 263 healthy controls, we examined the combined effects between CDK5R1 (3'-UTR, rs735555) and GSK-3beta (-50, rs334558) polymorphisms on susceptibility to AD.

Results

Subjects carrying both the CDK5R1 (3'-UTR, rs735555) AA genotype and the GSK-3beta (-50, rs334558) CC genotype had a 12.5-fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01-0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.

Conclusion

These data support a role for tau phosphorylation regulating genes in risk for AD."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.org/dc/terms/identifier"doi:10.1111/j.1600-0404.2008.01128.x"xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Combarros O."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Mateo I."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Berciano J."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Garcia-Gorostiaga I."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Infante J."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Sanchez-Juan P."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Rodriguez-Rodriguez E."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/author"Vazquez-Higuera J.L."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/name"Acta Neurol Scand"xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/pages"130-133"xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/title"Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3beta) and Alzheimer's disease risk."xsd:string
http://purl.uniprot.org/citations/19154537http://purl.uniprot.org/core/volume"120"xsd:string
http://purl.uniprot.org/citations/19154537http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19154537
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