Neuropathology of Down syndrome and Alzheimer disease

Abstract

Patients with Down syndrome (DS) over 40 years of age, prematurely and consistently develop neurofibrillary tangles (NFT), intracytoplasmic inclusions of highly insoluble straight or paired helical 12-16 nm filaments, and senile plaques (SP) composed of abnormal neurites surrounding a core of beta amyloid. These two lesions occur in distributions similar to those seen in Alzheimer disease (AD). SP and NFT are detected also in some younger individuals with DS (10-30+ years) when immunocytochemical and/or silver staining techniques are used. Retrospective and prospective attempts to relate neuropathological lesions and clinical dementia in DS have produced conflicting results. Clinical evidence of dementia and large numbers of SP and NFT were not always concordant. The predictable and consistent appearance of the AD-like neuropathologic changes in DS provides an unusual opportunity to examine the sequential development of SP and NFT. By combining morphological, immunocytochemical, and morphometric techniques with molecular biological approaches, the evolution of the structural and chemical changes in DS and AD can be examined and their relationship to clinical deficits can be evaluated.