Jørgensen O S, Brooksbank B W, Balázs R
Neuropsychiatric Institute, University of Copenhagen, Denmark.
J Neurol Sci. 1990 Aug;98(1):63-79. doi: 10.1016/0022-510x(90)90182-m.
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.
采用定量免疫化学方法，对阿尔茨海默病（AD）患者及唐氏综合征（DS）成人患者大脑皮质尸检样本中相对富集于神经元（神经细胞黏附分子（NCAM）和D3蛋白）或胶质细胞（谷氨酰胺合成酶、胶质纤维酸性蛋白（GFAP）和S100）的蛋白质进行了检测，后者也表现出阿尔茨海默型神经病理学的明显体征。AD和DS的变化趋势相似，但在后者中更为明显。星形胶质细胞的生化组成受到不同程度的影响：在额叶和DS颞叶皮质中，谷氨酰胺合成酶的特定浓度未改变，而S100和可溶性GFAP的浓度显著升高（分别约为对照值的260%和690%）。在AD额叶皮质中，谷氨酰胺合成酶的测定值正常，而S100和GFAP约为对照值的180%和230%。这些观察结果（谷氨酰胺合成酶正常而其他标志物水平升高）可能表明病理变化涉及一种分化的星形胶质细胞反应，且DS中的星形胶质细胞反应比AD中更明显。在DS中，S100的增加部分可由基因剂量效应解释，部分可由反应性胶质增生解释。神经元标志物也受到不同程度的影响。与适当对照相比，额叶皮质中D3蛋白的浓度在DS中降低了24%，在AD中降低了14%，而NCAM水平未受到显著影响。DS和AD中NCAM与D3蛋白的比率分别显著增加了32%和8.5%。这些观察结果与以下观点一致，即成熟神经元结构的破坏（以D - 3蛋白为标志）与新神经元膜的形成（以NCAM为指示）同时发生，即在这些退行性疾病中，大脑皮质神经元正在发生可塑性变化，其中营养物质可能起作用。
