Fig. 1: Integrative analysis to define genes and pathways dysregulated in FTLD with MAPT p.R406W.

Human iPSC-derived cortical neurons from MAPT p.R406W carriers and isogenic controls served as a discovery cohort to identify genes affected by the MAPT p.R406W mutation (n = 328). To define the genes that are differentially expressed in disease, we sought to replicate the differential expression analysis in human brains from MAPT p.R406W carriers and non-carrier controls. We identified 61 genes that were differentially expressed in both paradigms (FDR B-Y < 0.05). These 61 genes were then functionally annotated and interrogated animal models of FTLD-tau