Trisomy 21 (T21) causes Down syndrome and an early-onset form of Alzheimer’s disease (AD). In this issue, Wu et al utilized human induced pluripotent stem cells (hiPSCs) along with CRISPR-Cas9 gene editing to investigate the contribution of chromosome 21 candidate genes to AD-relevant neuronal phenotypes. Shown are representative immunostaining images of neurons derived from a T21 iPSC line (bottom panels) and a T21 iPSC line which lost one copy of HSA21 (top panels). IPSC-derived neurons are immunostained for bIII-tubulin (green, left panels), neurofilament heavy chain (NEFH, red, middle panels) and POU Class 3 Homeobox 2 (POU3F2, pink, right panels). Nuclei are stained with DAPI in all images. For more information, see pages 1970-1989. Images acquired by Elizabeth Vinton.