Interestingly, formation of neurofibrillary tangles or Aβ plaques is typically not seen in conventional two-dimensional cultures of AD-derived iPSC neurons, but filaments of aggregated tau can appear when AD neurons are cultured in three-dimensional systems, as demonstrated with AD neurons overexpressing mutant APP or PSEN1 (Choi et al., 2014). Here, APP is linked to Alzheimer disease.