Neurodevelopmental Abnormalities in Down Syndrome: Structural and Functional Brain Deficits

This review examines how trisomy 21 causes neurobiological changes in Down syndrome, including impaired synaptic plasticity, reduced gray matter, altered neurotransmission (excess GABA, reduced glutamate), and hippocampal dysfunction that underlie cognitive and motor deficits. The mechanisms discussed—synaptic abnormalities, neurodegeneration of cholinergic neurons, and cerebellar impairment—explain the learning, memory, and motor coordination challenges observed in individuals with Down syndrome.