The proteostasis and organelle homeostasis deficits we observed in human aged and AD tNeurons are accompanied by characteristic AD-related protein pathologies, including Aβ, pTau and TDP-43 deposits (Fig.1g, Extended Data Fig.3 and Extended Data Fig.5a,b) as well as inflammasome activation and cytokine secretion (Fig.5c,d and Extended Data Fig.12a). This evidence concerns the gene TARDBP and Alzheimer disease.