Solid trouble: tau and TDP-43 interaction in aggregation and pathology

Both microtubule-binding protein tau and RNA-binding protein TDP-43 have been associated with neurodegenerative diseases, such as Alzheimer’s disease, including in co-pathological deposition with each other, but how they interact biophysically and pathologically has been challenging to evaluate. In this issue of The EMBO Journal, Simonetti and colleagues show how tau and TDP-43 directly interact both in phase separation and pathologically associated seeding, resulting in enhanced TDP-43 aggregation.