To test if Sirt2 is required for Fzd1 and Fzd7 downregulation in AD, we established an AD cellular model: hippocampal primary neurons were cultured for 15DIV and treated overnight with Aβo (Figs. 3A, S2E), leading to Fzd1 and Fzd7 reduced expression, reduced H4K16ac and increased Sirt2 levels at their promoters and also synapse loss, without modulating total Sirt2 mRNA or protein levels (Fig. S2F–K). This evidence concerns the gene SIRT2 and Alzheimer disease.