CORRELATION OF ASTROCYTIC S100-BETA EXPRESSION WITH DYSTROPHIC NEURITES IN AMYLOID PLAQUES OF ALZHEIMERS-DISEASE

The neurite extension factor S100 beta is overexpressed by activated a strocytes associated with amyloid-containing plaques in Alzheimer's di sease, and has been implicated in dystrophic neurite formation in thes e plaques. This predicts (a) that the appearance of S100 beta-immunore active (S100 beta(+)) astrocytes precedes that of dystrophic neurites in diffuse amyloid deposits and (b) that the number of these astrocyte s correlates with the degree of dystrophic neurite proliferation in ne uritic plaques. As a rest of the first prediction, we determined the n umber of S100 beta(+) astrocytes associated with different plaque type s: diffuse non-neuritic, diffuse neuritic, dense-core neuritic, and de nse-core non-neuritic. Diffuse non-neuritic plaques had small numbers of associated S100 beta(+) astrocytes (1.3 +/- 0.1 S100 beta(+) astroc ytes per plaque [mean +/- SEM]; 80% of plaques had one or more). These astrocytes were most abundant in diffuse neuritic plaques (4.2 +/- 0. 2; 100%), were somewhat less numerous in dense-core neuritic plaques ( 1.6 +/- 0.2; 90%), and were only rarely associated with dense-core non -neuritic plaques (0.15 +/- 0.05; 12%). As a test of the second predic tion, we correlated the number of S100 beta(+) astrocytes per plaque w ith the area of beta-amyloid precursor protein (beta-APP) immunoreacti vity per plaque (an index of the size of the plaques' dystrophic neuri te shells) and found a significant positive correlation (r = 0.74, p < 0.001). This correlation was also evident at the tissue level: the nu mbers of S100 beta(+) astrocytes per plaque-rich field correlated with the total area of beta-APP immunoreactivity in these fields (r = 0.66 , p < 0.05). These correlations support the idea that astrocytic activ ation and S100 beta overexpression are involved in the induction and m aintenance of dystrophic neurites in amyloid deposits, and support the concept of a glial cytokine-mediated cascade underlying the progressi on of neuropathological changes in Alzheimer's disease.