Abstract
Down syndrome (DS) is a genetic intellectual disorder caused by trisomy of chromosome 21 (Hsa21) and presents with a variety of phenotypes. The correlation between the chromosomal abnormality and the resulting symptoms is unclear, partly due to the spectrum of impairments observed. However, it has been determined that trisomy 21 contributes to neurodegeneration and impaired neurodevelopment resulting from decreased neurotransmission, neurogenesis, and synaptic plasticity. DS is linked to synaptic abnormalities and hindered hippocampal neuron development as well. Altered synaptic plasticity in the hippocampus decreases long-term potentiation, leading to short- and long-term learning and memory deficits. Individuals with DS show reduced gray matter, which affects cerebral cortex structure and impairs coordination and thought. Neurotransmitter excess, such as increased gamma-aminobutyric acid (GABA) release, causes over-inhibition and contributes to cognitive deficits. This inhibition also affects hippocampal synaptic plasticity. Additionally, DS often involves neurodegeneration of cholinergic neurons in the basal forebrain, further impairing learning and memory. Reduced glutamate transmission and decreased amyloid precursor protein metabolism contribute to synaptic plasticity deficits and behavioral changes in DS. Decreased neurotransmission, diminished motor neurons, and impaired cerebellar and cerebral development are the main causes of motor deficits in DS. This review discusses the stark structural changes in DS and their functional consequences.