TARDBP and proteostasis deficiencies: To model TDP-43-associated proteinopathies, we used CRISPR-mediated gene editing to introduce the ALS/FTD-associated K181E mutation at the endogenous TARDBP locus in a well-characterized dementia genetic risk-free iPSC line followed by extensive whole exome sequencing to rule out CRISPR mediated off target effect (see method and table S6).