Semaglutide ameliorates Alzheimer's disease and restores oxytocin in APP/PS1 mice and human brain organoid models.

AIMS: To investigate the therapeutic effects and mechanisms of Semaglutide in Alzheimer's disease (AD), and identify its potential targets.

METHODS

We systematically evaluated the effect of Semaglutide on Alzheimer's disease (AD), using both mice and human organoid models.

RESULTS

Behavioral analyses on APP/PS1 mice demonstrated that Semaglutide improved the cognitive capabilities, particularly in the learning and memory domains. Biochemical investigations further highlighted its role in reducing amyloid plaque deposition and down-regulating the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) expression in the mouse brain tissues. Meanwhile, oxytocin (OXT) was up-regulated after Semaglutide treatment. Subsequent studies using human AD-brain organoids (BOs) models revealed that, upon Semaglutide treatment, these AD-BO models also exhibited reduced levels of amyloid-beta (Aβ), phosphorylated Tau (p-Tau) and GFAP expression as well as increased OXT level.

CONCLUSIONS

Semaglutide can ameliorate Alzheimer's disease in pre-clinical models, suggesting the promising therapeutic potential in AD patients.