Classical in vitro models for PD are mainly comprised of PD‐patient fibroblasts or immortalized cells (e.g., SH‐SY5Y) with all the associated drawbacks, including different gene expression, compared to neurons.26 The successful use of 3D‐derived and hNESC‐derived neurons for phenotype assessment has been demonstrated with Alzheimer's disease.9 As paracrine factors diffuse rapidly into large media volumes in 2D cultures, we hypothesized that neurons cultivated in 3D exacerbated LRRK2‐G2019S toxicity by providing a brain tissue‐like environment. The gene discussed is LRRK2; the disease is early-onset autosomal dominant Alzheimer disease.