Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3beta (GSK-3B) phosphorylates tau protein, and increased GSK-3B expression has been associated with neurofibrillary tangles. To determine whether polymorphisms in the GSK3B gene and microtubule associated protein tau (MAPT) gene underpin susceptibility to late-onset Alzheimer's disease (LOAD), we conducted a case-control study in a Chinese cohort of 257 LOAD cases and 326 healthy controls matched for sex and age. The minor allele (T) of the promoter rs334558 within GSK3B was associated with an increased risk of LOAD (odds ratios/OR=1.381, P=0.006), T carriers may be easier to develop AD (P=0.002, power=0.92). And the association was influenced by the presence of ApoE ε4 allele. Moreover, it showed a highly significant synergistic interaction with the ApoE ε4 allele (OR=3.782, P<0.001). All subjects in this study were identified as H1 MAPT haplotype. Haplotype analysis revealed that, the -157T/-50T haplotype significantly increased the risk of developing AD (OR=1.383, P=0.013). Our findings suggest that the functional polymorphisms in GSK3B promoter may be involved in the risk of developing sporadic LOAD in Han Chinese.
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