Hatanpää K, Chandrasekaran K, Brady D R, Rapoport S I
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892-1582, USA.
Brain Res Mol Brain Res. 1998 Aug 15;59(1):13-21. doi: 10.1016/s0169-328x(98)00117-x.
It has been proposed that neuritic plaques or toxic substances diffusing from them contribute to neurodegeneration in Alzheimer disease. We examined this hypothesis by looking for evidence of decreased neuronal energy metabolism in the proximity of neuritic plaques. Levels of mitochondrial DNA-encoded mRNA for subunit III of cytochrome oxidase, a marker of neuronal energy metabolism, were determined in post mortem brain samples. Consistent with earlier results, overall cytochrome oxidase subunit III mRNA levels were decreased in Alzheimer midtemporal cortex compared with controls. However, this reduction did not correlate with plaque density. In Alzheimer brains, cytochrome oxidase subunit III mRNA levels in neurons bearing neurofibrillary tangles were lower than in tangle-free neurons. However, neuronal cell bodies in close proximity of neuritic plaques showed no decrease in cytochrome oxidase subunit III mRNA or total polyadenylated mRNA compared with more distant neurons. Cytochrome oxidase enzyme activity in neuronal processes also showed no local reduction around neuritic plaques. These results suggest that neuritic plaques do not contribute to reduced neuronal energy metabolism in Alzheimer disease.
有人提出，神经炎斑或从它们扩散出的有毒物质会导致阿尔茨海默病中的神经退行性变。我们通过寻找神经炎斑附近神经元能量代谢降低的证据来检验这一假设。在死后脑样本中测定了细胞色素氧化酶亚基III的线粒体DNA编码mRNA水平，细胞色素氧化酶亚基III是神经元能量代谢的标志物。与早期结果一致，与对照组相比，阿尔茨海默病中颞叶皮质的细胞色素氧化酶亚基III mRNA总体水平降低。然而，这种降低与斑块密度无关。在阿尔茨海默病大脑中，带有神经原纤维缠结的神经元中的细胞色素氧化酶亚基III mRNA水平低于无缠结的神经元。然而，与距离较远的神经元相比，靠近神经炎斑的神经元细胞体中细胞色素氧化酶亚基III mRNA或总多聚腺苷酸化mRNA没有减少。神经元突起中的细胞色素氧化酶活性在神经炎斑周围也没有局部降低。这些结果表明，神经炎斑不会导致阿尔茨海默病中神经元能量代谢降低。
