Experimental validation of candidate AD treatments identified by multi-OMICS analyses and real-world clinical evidence

在这个正在进行的项目中，我们对大约30种候选AD治疗药物进行了详细的基于细胞培养的表型筛选。这些实验检测了与AD相关的特定分子结果，包括β-淀粉样蛋白1-42毒性，ii)β-淀粉样蛋白1-42清除，β-淀粉样蛋白1-42分泌，Tau聚集，Tau磷酸化，神经炎症和轴突生长。然后，通过对APP/PS1小鼠海马片晚期长时程增强的电生理记录，测试对这些分析产生有益影响的药物是否有能力挽救受损的突触可塑性。

In this ongoing project, we have performed detailed cell culture based phenotypic screening on approximately 30 drugs nominated as candidate AD treatments. These experiments assay specific molecular outcomes relevant to AD including beta-amyloid 1-42 toxicity, ii) beta-amyloid 1-42 clearance, beta-amyloid 1-42 secretion, Tau aggregation, Tau phosphorylation, Neuroinflamamtion and Neurite outgrowth. Drugs that exert a beneficial effect on these assays are then tested for their ability to rescue impaired synaptic plasticity through electrophysiological recordings of late long-term potentiation of hippocampal slices from APP/PS1 mice.