G2Cdb::Human Disease report

Disease id
D00000194
Name
Alzheimer's disease (late onset)
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001420 GSK3B
glycogen synthase kinase 3 beta
Y (11326302) Single nucleotide polymorphism (SNP) N

References

  • Identification of sequence variants and analysis of the role of the glycogen synthase kinase 3 beta gene and promoter in late onset Alzheimer's disease.

    Russ C, Lovestone S and Powell JF

    Department of Neuroscience, Institute of Psychiatry, London SE5 8AF, UK.

    Alzheimer's disease (AD) is a disorder characterised by a progressive deterioration in memory and other cognitive functions. Glycogen synthase kinase 3 beta (GSK3 beta) phosphorylates the microtubule associated protein tau at sites that are aberrantly phosphorylated in AD. GSK3 beta binds to presenilin 1 and plays a role in wnt and insulin signalling cascades, both of which have been proposed to be linked to AD. Moreover GSK3 beta activity may be altered in AD brain. These observations suggest a central role for GSK3 beta in AD and led us to investigate GSK3 beta as a candidate gene for AD. We sought to identify sequence variations in the gene and its promoter, as these could have an effect on activity and expression leading to abnormal function. Sequencing over 3000 bp of the GSK3 beta putative promoter revealed there to be five sequence variations, two of which were common (>10%). However on further examination none of these, either alone or in synergy, had any association with late onset AD. Stratification of the data by APOE epsilon 4 status also produced no significant association. Sequencing of the GSK3 beta coding region revealed no variations. This would suggest that the aberrant phosphorylation of tau by GSK3 beta in AD is not due to sequence variations in the gene or its promoter.

    Molecular psychiatry 2001;6;3;320-4

Literature (1)

Pubmed - human_disease

  • Identification of sequence variants and analysis of the role of the glycogen synthase kinase 3 beta gene and promoter in late onset Alzheimer's disease.

    Russ C, Lovestone S and Powell JF

    Department of Neuroscience, Institute of Psychiatry, London SE5 8AF, UK.

    Alzheimer's disease (AD) is a disorder characterised by a progressive deterioration in memory and other cognitive functions. Glycogen synthase kinase 3 beta (GSK3 beta) phosphorylates the microtubule associated protein tau at sites that are aberrantly phosphorylated in AD. GSK3 beta binds to presenilin 1 and plays a role in wnt and insulin signalling cascades, both of which have been proposed to be linked to AD. Moreover GSK3 beta activity may be altered in AD brain. These observations suggest a central role for GSK3 beta in AD and led us to investigate GSK3 beta as a candidate gene for AD. We sought to identify sequence variations in the gene and its promoter, as these could have an effect on activity and expression leading to abnormal function. Sequencing over 3000 bp of the GSK3 beta putative promoter revealed there to be five sequence variations, two of which were common (>10%). However on further examination none of these, either alone or in synergy, had any association with late onset AD. Stratification of the data by APOE epsilon 4 status also produced no significant association. Sequencing of the GSK3 beta coding region revealed no variations. This would suggest that the aberrant phosphorylation of tau by GSK3 beta in AD is not due to sequence variations in the gene or its promoter.

    Molecular psychiatry 2001;6;3;320-4

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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