Topographical Comparison of Lesions in Trisomy 21 and Alzheimer’s Disease: A Study with PET, Anatomical and Neuropathological Investigations

Recent evidence suggests that Alzheimer’s disease (AD) is a clinically heterogeneous disorder and that specific subgroups exist. A human model of AD exists that avoids such problems as heterogeneity. Down’s syndrome (DS), trisomy 21, is a genetic disorder in which an extra portion of chromosome 21 leads to mental retardation, short stature, and phenotypic abnormalities. DS subjects over 35 years of age demonstrate neuropathological and neurochemical defects postmortem which are virtually indistinguishable from those found in brain of AD patients, as well as a universal cognitive deterioration and a 20%–30% prevalence of dementia. In older DS subjects and AD patients, positron emission tomography (PET) shows identical patterns of abnormal glucose metabolism, selectively involving association areas of frontal, parietal and temporal neocortices, but sparing primary sensory and motor regions. In demented DS as well as AD patients, furthermore, quantitative computer assisted tomography (CT) indicates accelerated neuronal loss and brain atrophy.