However, Ovchinnikov and colleagues (2018) have demonstrated that despite the deletion of the supernumerary copy of the APP gene in an isogenic DS human model (where they deleted the supernumerary copy of the APP gene in trisomic Down syndrome induced pluripotent stem cells or upregulated APP expression in euploid human pluripotent stem cells using CRISPRa) tau pathology still emerged. Here, APP is linked to Down syndrome.