Morphometric analysis was used to measure cross-sectional areas of cerebral structures in middle-aged patients with Down's syndrome (Nequals;5) for comparison with data obtained from individuals with senile dementia of the Alzheimer type (Nequals;16) and neuropathologically normal controls (Nequals;14). Down's syndrome was distinguished from Alzheimer's disease by the 19percnt; lower mean brain weight which was associated with more pronounced reductions in the areas of both cortex and white matter. However, the differences were most striking in the anterior frontal and anterior temporal regions where the effects of arrested neurodevelopment are grossly evident. In addition, in Down's syndrome the amygdala was significantly smaller than in Alzheimer's disease. In both Down's syndrome and Alzheimer's disease, shrinkage of the cortical ribbon was associated with abundant neuritic plaques and neurofibrillary tangles, while white matter atrophy was associated with histopathological evidence of axonal degeneration. These findings suggest that in Down's syndrome the reduction in volume in the posterior portion of the cerebrum relative to controls is largely due to acquired lesions of Alzheimer's disease, whereas anteriorly and within certain subcortical nuclei, the effects of both Alzehimer's disease and arrested neurodevelopment are manifested. Moreover, the finding of white matter lesions in Down's syndrome corroborates the notion that white matter degeneration is a fundamental component of the Alzheimer's disease process.
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