Compared with untreated cells in the NFκB and TGFβ panels, the expression of histone deacetylase 4 (HDAC4), a global regulator for the transcription of genes involved in synaptic plasticity, neuronal survival, and neurodevelopment (43), as well as the function of SMAD1 and SMAD2, showed dramatic increase by AD TauO (Figs. 6, D, E, I and J and S4, D and E). Here, SMAD2 is linked to Alzheimer disease.