14-3-3 zeta and tau genes interactively decrease Alzheimer's disease risk.

Abnormal tau hyperphosphorylation has been suggested as being one of the central events in the development of neurofibrillary tangles, which are one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains. 14-3-3 zeta protein is associated with tau in brain and stimulates tau phosphorylation. In a case-control study in 293 AD patients and 396 healthy controls, we examined whether the combined gene effects between 14-3-3 zeta (intron 4, rs 983583) polymorphism and tau (intron 9, rs 2471738) polymorphism might be responsible for susceptibility to AD. Subjects carrying both the 14-3-3 zeta (intron 4, rs 983583) AA and the tau (intron 9, rs 2471738) CC genotypes had a two and a half times lower risk of developing AD than subjects without these risk genotypes (OR = 0.4, 95% CI = 0.2-0.8, p = 0.016). Considering synergistic effects between polymorphisms in tau phosphorylation related genes may help in determining the risk profile for AD.