Nature Aging：宋伟宏/张韵团队揭示GLP-1类减肥药防治阿尔茨海默病新机制

Core Viewpoint - The article discusses the potential neuroprotective effects of GLP-1 receptor agonists (GLP-1RAs) like semaglutide and tirzepatide in reducing the risk of Alzheimer's disease (AD) in patients with type 2 diabetes, highlighting a recent study that elucidates the underlying molecular mechanisms [2][3][8]. Group 1: Research Findings - GLP-1RAs activate the AMPK signaling pathway, significantly reducing core pathological features of Alzheimer's disease and effectively improving cognitive dysfunction [3][5]. - In Alzheimer's disease model mice, plasma GLP-1 levels were found to be decreased, and in AD patients, GLP-1 levels were negatively correlated with β-amyloid (Aβ) burden [6]. - The study demonstrated that enhancing GLP-1 signaling through GLP-1RAs (using exenatide or tirzepatide) increases CaMKK2-AMPK signaling, thereby reducing the generation of Aβ through the inhibition of β-secretase 1 (BACE1) [6][8]. Group 2: Implications for Treatment - The findings provide critical experimental evidence for the clinical application of GLP-1RAs in the prevention and treatment of Alzheimer's disease, potentially leading to expanded clinical trials and indications [8].