Especially, hyperglycemia induced the decreased expression of cytoplasmic SIRT1 only on the 3D platform with Aß accumulation and Tau phosphorylation in neurons, which was recovered upon glucose level stabilization; however, there were no notable changes in cells cultured in 2D Transwell plates (Figure 3 and Figure S5, Supporting Information). This evidence concerns the gene MAPT and Hyperglycemia.