We have determined that downregulation of WWOX leads to the aggregation of TPC6AΔ, TIAF1, tau and Aβ in vitro and in vivo.1,7–9 Sequentially, upon WWOX downregulation, TPC6AΔ becomes aggregated first, followed by TIAF1 aggregation, caspase activation, APP degradation for Aβ generation, as well as tau tangles formation.1,7–9 The observations suggest a critical role of WWOX in regulating protein aggregation and AD progression. Here, WWOX is linked to Alzheimer disease.