Bazedoxifene restores myelin changes and attenuates cognitive deficits in a mouse model of Alzheimer's disease
Man-Yu Xu, Yu-Di Bai, Xiao-Qin Zeng, Cheng-Rong Tan, Yu-Jie Lai, Yan-Jiang WangBackground
Demyelination and remyelination are critical processes in the pathogenesis of Alzheimer's disease (AD). The selective estrogen receptor modulator bazedoxifene (BZA) has been shown to promote remyelination, suggesting its potential therapeutic efficacy.
Objective
This study aimed to evaluate the therapeutic efficacy of BZA in addressing demyelination and associated cognitive deficits in a mouse model of AD.
Methods
The changes in myelin and oligodendrocyte-related indicators in the brains of APP/PS1 mice were assessed via immunostaining. 5 × FAD transgenic mice received oral administration of BZA or vehicle for 3 months. The therapeutic outcomes were evaluated through behavioral tests, immunostaining and western blotting.
Results
AD mice exhibited pronounced myelin loss and oligodendrocytes depletion. BZA treatment attenuated cognitive decline, restored myelin changes and mitigated neurodegeneration in the brain. These effects were observed independently of alterations in amyloid-β deposition.
Conclusions
These findings provide compelling evidence supporting the involvement of demyelination in AD and suggest that BZA may represent a promising therapeutic agent for AD by targeting myelin repair mechanisms.