To improve on cell culture models of disease, interest has turned to 3D cultures. Recently, a brain tissue-like 3D environment was created to cultivate AD pathology development in 3D neuronal culture with some important findings [14]. In traditional 2D cell culture, secreted Aβ species diffuse into the large volume of the cell culture media precluding accumulation of Aβ when the media are routinely changed. In 3D cultures, local Aβ concentrations are apparently high enough to initiate Aβ aggregation and accelerate Aβ deposition. Choi et al reported a deposition of Aβ aggregates in neurons in thin-layer 3D cultures that were differentiated for only 6 weeks [14]. In addition to Aβ aggregation, phosphorylated Tau protein also accumulated, suggesting that both of these processes are accelerated by 3D culture conditions. These results suggest that 3D culture conditions hold great promise for recapitulating Aβ and Tau pathologies and allowing testing of candidate treatments aimed at key pathogenic steps that are not present in 2D cultures. In order to employ these models for AD drug testing, 3D cultures must be carefully assessed for cell behavior, secretase activity, drug penetration, and other factors related to extracellular matrix and the potential for addition of glial cells.
