Sulforaphane Inhibits the Generation of Amyloid-β Oligomer and Promotes Spatial Learning and Memory in Alzheimer's Disease (PS1V97L) Transgenic Mice

Abnormal amyloid-beta (A beta) aggregates are a striking feature of Alzheimer's disease (AD), and A beta oligomers have been proven to be crucial in the pathology of AD. Any intervention targeting the generation or aggregation of A beta can be expected to be useful in AD treatment. Oxidative stress and inflammation are common pathological changes in AD that are involved in the generation and aggregation of A beta. In the present study, 6-month-old PS1V97L transgenic (Tg) mice were treated with sulforaphane, an antioxidant, for 4 months, and this treatment significantly inhibited the generation and aggregation of A beta. Sulforaphane also alleviated several downstream pathological changes that including tau hyperphosphorylation, oxidative stress, and neuroinflammation. Most importantly, the cognition of the sulforaphane-treated PS1V97L Tg mice remained normal compared to that of wild-type mice at 10 months of age, when dementia typically emerges in PS1V97L Tg mice. Pretreating cultured cortical neurons with sulforaphane also protected against neuronal injury caused by A beta oligomers in vitro. These findings suggest that sulforaphane may be a potential compound that can inhibit A beta oligomer production in AD.