Aging in Down syndrome (DS) is accompanied by neuropathological features of Alzheimer's disease (AD). Therefore, DS has been proposed as a model to study predementia stages of AD. MRI-based measurement of grey matter atrophy is an in vivo surrogate marker of regional neuronal density. A range of neuroimaging studies have described the macroscopic neuroanatomy of DS. Recent studies using sensitive quantitative measures of region-specific atrophy based on high-resolution MRI suggest that age-related atrophy in DS resembles the pattern of brain atrophy in early stages of AD. The pattern of atrophy determined in predementia DS supports the notion that AD-type pathology leads to neuronal degeneration not only in allocortical, but also in neocortical brain areas before onset of clinical dementia. This has major implications for our understanding of the onset and progression of AD-type pathology both in DS and in sporadic AD.