MAPT and Alzheimer disease: Interestingly, neutral sphingomyelinase 2 (nSMase 2) inhibition using GW4869 or genetic deletion, resulting in blockage of EV formation and subsequent release from multivesicular bodies (MVBs), was shown to be beneficial in mitigating AD pathology in 5xFAD mice [36, 37] and reduced tau propagation in a mouse model of rapid tau propagation [38].