Overexpression of s100beta in Down's syndrome: correlation with patient age and with beta-amyloid deposition.

ABSTRACT

S100beta is an astrocyte-derived uritotrophic' cytokine which has been implicated in the pathogenesis of Alzheimer's disease. S100beta overexpression by plaque-associated astrocytes correlates with growth of abnormal (strophic') neurites in beta-amyloid plaques, one of the major neuropathological hallmarks of Alzheimer's disease. As the characteristic neuropathological changes of Alzheimer's disease are virtually universal in middle-aged Down's syndrome patients, studies of Down's syndrome patients provide a unique opportunity to investigate the pathophysiological processes underlying the development of Alzheimer-type neuropathological changes. Computerized morphometric analysis was used to quantify astrocyte activation and astrocytic expression of S100beta, and to correlate these with beta-amyloid deposition, in a clinically well-characterized cohort of Down's syndrome subjects, aged 13-65 years. There were significant positive correlations between S100beta expression and patient age, and between S100beta expression and cerebral cortical beta-amyloid deposition. Moreover, the numbers of activated (enlarged) astrocytes overexpressing S100beta showed a significant correlation with the numeric density of beta-amyloid plaques, from the youngest to the oldest ages and within age ranges where pathology is most florid, while no such relationship was found between the numbers of small, non-activated S100beta-immunoreactive cells and numerical density of beta-amyloid plaques. These correlations, together with established functions of S100beta, are consistent with the idea that S100beta overexpression promotes beta-amyloid plaque formation and progression in Down's syndrome.