Age-related changes in the density and morphology of plaques and neurofibrillary tangles in Down syndrome brain

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Abstract
Fifteen cases of Down syndrome between age 25–59 years were examined neuropathologically. A variety of histological methods were used to identify plaques and neurofibrillary tangles (NFT). All cases had some plaques or NFT, but their density was generally not high before the age of 40 years. Plaques and NFT tended to appear at about the same time although in somewhat different cortical areas. Changes appeared first in the dentate gyrus, subiculum, entorhinal and association neocortex. The stages in the evolution of plaque morphology were quantitated in the dentate gyrus. The earliest change was the extracellular accumulation of fibrillar material with the histological characteristics of amyloid. In the second stage there was an exuberant neuritic reaction with swollen processes that contained little or no paired helical filaments (PHF). Stage 1 and 2 plaques were seen predominantly between ages 25–38 years, and were not obviously associated with blood vessels or glial cells. In the third stage of plaque formation neurites appeared to degenerate, contained more PHF, and surrounded a compact core of amyloid. Stage 3 plaques were never very numerous, and were seen only between ages 48–55 years. Stage 4 plaques consisted of a cloud of silver-positive debris. They appeared to be the final stage and were the predominant morphological type in the dentate gyrus after age 48 years. Amyloid angiopathy was present only after age 48, and was a prominent finding in only three cases.