Abnormal neuronal and synaptic morphology in Down syndrome brains reproduces in human isogenic cellular models

Researchers used human induced pluripotent stem cells to model Down syndrome (trisomy 21) and found that trisomic neurons display abnormal morphology including shorter, thicker neurites with fewer branches, reduced neuronal network formation, and altered synaptic markers compared to normal neurons. These cellular abnormalities mirrored findings in actual Down syndrome brain tissue and were accompanied by mitochondrial dysfunction and reduced neural proliferation.