The use of three murine genetic models of Alzheimer's disease reveals efficacy of 4',5,7-trihydroxyisoflavone in alleviating cognitive deficits and reducing levels of amyloid-beta and hyperphosphorylated tau protein.

BACKGROUND

Despite intensive studies on developing therapies for Alzheimer's disease (AD), there is still a need to improve the treatment efficacy. Results of recent studies indicated that genistein (4',5,7-trihydroxyisoflavone) was effective in an autophagy stimulation-dependent improving of cognitive deficits and reducing levels of amyloid-beta and hyperphosphorylated tau protein in brains, when employing a streptozotocin-induced rat model of the sporadic form of AD. Despite those encouraging results, the above-mentioned model has its limitations, mainly related to the rapid and inducible character of the symptoms caused by streptozotocin, induction of other effects (like diabetes) by this toxin, and the requirement for invasive administration of this compound to the brain, in contrast to naturally occurring AD. Thus, in this study, we hypothesized that genistein might be effective in reducing symptoms of AD in well-defined genetic models of this disease and tested the efficacy of this compound.

RESULTS

Three genetic models of AD were employed, including mouse lines 5xFAD, THY-Tau22, and 3xTg-AD. Orally administered genistein (at the dose of 150 mg/kg/day) considerably alleviated cognitive deficits (in spatial memory, learning, and long-term memory) of AD animals as estimated using the Morris water maze and the novel object recognition tests. Moreover, significantly reduced levels of amyloid-beta and hyperphosphorylated tau protein in plasma and brains were detected in genistein-treated AD animals relative to those treated with water.

CONCLUSIONS

We conclude that genistein revealed significant efficacy in ameliorating symptoms occurring in murine genetic models of AD. Thus, further studies towards the development of a genistein-based treatment for this disease are substantiated.

CLINICAL TRIAL NUMBER: Not applicable.