However, when TPC6AΔ undergoes excessive aggregation in the mitochondria, activation of caspases occurs that leads to apoptosis.1,7,30 TGF-β/Smad signaling has a critical role in the pathogenesis of AD.7,31,32 TGF-β1 expression is upregulated in a transgenic mouse model of familial Alzheimer's disease, and this leads to neuronal apoptosis.32 How WWOX interacts with TPC6A under the effect of TGF-β1 was examined by co-immunoprecipitation (co-IP) and time-lapse microscopy with Förster (fluorescence) resonance energy transfer (FRET) analysis.22,28,33,34. The gene discussed is TGFB1; the disease is familial Alzheimer disease.