As shown here and previously [9–11,22], both oTau and SτAs mimic the LTP disruptive action of synaptotoxic tau in patient-derived brain extracts [9,11,22] and extracellular tau in secretomes of induced pluripotent stem cell-derived neurons from individuals with trisomy 21, the most common genetic cause of AD [36], but see [37]. Here, MAPT is linked to trisomy 21.