β-Sitosterol treatment attenuates cognitive deficits and prevents amyloid plaque deposition in amyloid protein precursor/presenilin 1 mice

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated beta-amyloid (A beta). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol beta-Sitosterol has a potential role in inhibiting the production of platelet A beta, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of beta-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with beta-Sitosterol for four weeks, from the age of seven months. Brain A beta metabolism was evaluated using ELISA and Western blotting. We found that beta-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. beta-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of beta-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that beta-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases A beta deposition.