Neuronal plasticity and astrocytic reaction in Down syndrome and Alzheimer disease

Proteins relatively enriched in neurons (neural cell adhesion molecule (NCAM) and D3-protein) or in glia (glutamine synthetase, glial fibrillary acidic protein (GFAP) and S100) were measured by quantitative immunochemical methods in autopsy samples of the cerebral cortex of subjects with Alzheimer disease (AD) and adults with Down syndrome (DS), the latter also presenting manifest signs of Alzheimer type of neuropathology. The trend of changes was similar in AD and DS, but more marked in the latter. The biochemical make-up of astrocytes was differentially affected: in both the frontal and DS temporal cortex the specific concentration of glutamine synthetase was unaltered, while that of S100 and the soluble form of GFAP was markedly elevated (about 260% and 690% of control values, respectively). In the AD frontal cortex the estimates for glutamine synthetase were normal, while S100 and GFAP were about 180% and 230% of control. The observations (normal GS and elevated levels of the other markers) might suggest that the pathological changes involve a differentiated astrocytic reaction and that the astrocytic reaction is more marked in DS than in AD. In DS the increase in S100 could be explained, in part, by a gene dosage effect and in part by reactive gliosis. The neuronal markers were also differentially affected. In comparison with appropriate controls, the concentration of D3-protein in frontal cortex was decreased by 24% in DS and by 14% in AD, whereas NCAM levels were not significantly affected. The ratio of NCAM to D3-protein was significantly increased by 32% and 8.5% in DS and AD, respectively. These observations are consistent with the view that the destruction of mature neuronal structures (as marked by the D-3 protein) coincides with the formation of new neuronal membranes (as indicated by NCAM), i.e. in these degenerative disorders plastic changes are taking place involving cerebral cortex neurons in which trophic substances may be instrumental.