PubMed1991
The brain of a child with Down syndrome develops differently from a normal one, attaining a form reduced in size and altered in configuration. Directly related to the mental retardation are neuronal modifications manifest as alterations of cortical lamination, reduced dendritic ramifications, and diminished synaptic formation. However, selected cholinergic marker enzymes such as choline acetyl transferase and acetyl cholinesterase have shown no alterations in young children with Down syndrome. The pace of the neuronal transformations is related to stage of maturation. With early growth and development, the normal dendritic tree continuously expands. In Down syndrome, at 4 months of age, the neurons show a relatively expanded dendritic tree, but during the first year the dendrites stop growing and become atrophic relative to control neurons. Accompanying these neuronal irregularities are subtle alterations of other cell types: astrocyte, oligodendrogliocyte, microglia, and endothelial cell. In early infancy, one of the astrocytic markers, GFAP, is not altered, but there is greater expression of S-100 protein in the temporal lobe in Down syndrome. Oligodendrogliocyte dysfunction is reflected in delayed myelination in pathways of frontal and temporal lobes. Microglia appear more prominent in Down syndrome. A minority of children with Down syndrome have vascular dysplasias and focal calcification of basal ganglia. In young children, expression of beta-amyloid in Down syndrome is no different than in normal children but disappears after age two, only to reappear in adults. As some of these studies suggest, the identification of genes on chromosome 21 and the determination of the gene product allow the production of specific antibodies and, through immunohistochemical techniques, the identification of the expression of these proteins in both normal development and Down syndrome. Specifically, the localization and appearance in development of proteins such as the beta-subunit of S-100, beta-amyloid (A4 protein), superoxide dismutase, and OK-2 are providing the means for better understanding the morphogenesis of the cellular and eventually molecular basis for the mental retardation in Down syndrome.