Molecular Mechanism of Dexmedetomidine in Alzheimer's Disease: Machine Learning Identifies RGS7 as a Key Therapeutic...

This study identifies RGS7 as a pivotal therapeutic target for dexmedetomidine (DEX) in Alzheimer's disease (AD). Bioinformatics revealed RGS7 is downregulated in AD, and in vivo, DEX administration in APP/PS1 mice restored its hippocampal expression and reduced Aβ plaque burden. Molecular docking supports a direct DEX-RGS7 interaction. The study links RGS7 to neuroinflammation, showing AD patients have elevated pro-inflammatory M1 macrophages and reduced follicular helper T cells. RGS7 expression negatively correlates with M1 macrophages and positively with follicular helper T cells. Crucially, RGS7 was found in microglia, suggesting DEX acts via RGS7 within these cells to exert its anti-inflammatory effects. With diagnostic potential (AUC = 0.79), the DEX-RGS7 axis is a promising therapeutic pathway for AD.