Recent work has implicated nuclear dysfunction of RNA-binding proteins as a driver of neurodegeneration in model organisms and cellular systems [5–8]. RNA acts as a potent initiator of tau aggregation in vitro and can decorate fibrillar tau after aggregation [9–11]. Most recently, tau has been shown to form aggregates with an RNA protein assembly in some cellular contexts [7]. The recruitment of RNA to tau aggregates may drive splicing defects or disrupt other nuclear functions related to RNA [5–7, 12]. These observations suggest the possibility of tauopathy-driven RNA-mediated cellular dysfunction, but these phenomena have not been investigated in the context of AD pathology. Here, we begin to address the role of RNA binding protein involvement with pathological tau in AD, guided by findings from molecular genetic investigations in model systems.
