A protective role for APP in nuclear waste clearance via lysosomal exocytosis

However, its physiological function remains incompletely understood. Here, we uncover a protective role for full-length APP in facilitating the disposal of nuclear-derived debris under genotoxic stress.

In both cultured cells and in vivo mouse models, loss of APP leads to nuclear waste accumulation, increased inflammation, and cell death, whereas APP overexpression mitigates these effects. Mechanistically, we show that APP supports the extracellular release of nuclear material through lysosomal exocytosis. APP mutants associated with familial AD fail to mediate this process.