The location and complexity of the nervous tissue and the feasibility of human-specific studies make it extremely difficult to identify the causes of neurodegenerative diseases and to find a cure for them. In order to improve the translatability of results in the drug discovery process, it is definitely advisable to use preclinical human-specific models. The in vitro use of relevant human cell types also allows the analysis of aspects of neurodegenerative diseases that cannot be examined in patients or animal models. These modern, stem cell-based (iPSC-based) platforms have several key advantages over traditional animal models. Despite these advantages, several technological challenges remain to be addressed, such as the difficulty in generating well-defined and physiologically homogeneous neuronal populations in the methods used to generate human neurons with cortical identity from induced pluripotent stem cells. Another limitation is that these test systems are usually used as two-dimensional (2D) monolayer cell cultures, thus lacking the characteristic and highly interconnected 3D environment of human brain tissue in terms of cell diversity and connectivity, as well as tissue development.