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 (Abeta). 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 Abeta, 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 Abeta 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 Abeta deposition.