Cottrell D A, Blakely E L, Johnson M A, Ince P G, Turnbull D M
Department of Neurology, The Medical School, University of Newcastle upon Tyne, UK.
Neurology. 2001 Jul 24;57(2):260-4. doi: 10.1212/wnl.57.2.260.
To determine whether hippocampal neurons and choroidal epithelial cells demonstrate a mitochondrial enzyme deficiency in AD more frequently than in normal aging.
High levels of mutant mitochondrial DNA (mtDNA) cause a deficiency in cytochrome c oxidase (COX) (complex IV activity) because three of its 13 subunits are encoded for by mtDNA. In contrast, succinate dehydrogenase (SDH) (complex II activity) remains intact because all of its subunits are nuclear encoded. The histologic hallmark of cells containing high levels of mtDNA mutation in both primary mtDNA disorders and normal aging muscle is the presence of COX-deficient SDH-positive cells.
The authors applied a sequential histochemical method for COX and SDH to hippocampal sections in 17 AD and 17 age-matched control brains. This confers the advantages of both looking at individual cells in situ and measuring the actual mitochondrial complex activity rather than simply the complex quantity.
COX-deficient SDH-positive hippocampal neurons and choroidal epithelial cells are more prevalent in patients with AD than in controls. In addition the COX-deficient SDH-positive choroidal cells are associated with an enlargement in size.
This increase in number of COX-deficient SDH-positive hippocampal pyramidal neurons and choroid epithelial cells provides strong evidence that a substantial mitochondrial enzyme activity defect occurs in individual cells more frequently in AD than in normal aging and that mitochondria may play a significant role in the pathogenesis of AD.
确定与正常衰老相比，海马神经元和脉络膜上皮细胞在阿尔茨海默病（AD）中是否更频繁地表现出线粒体酶缺乏。
高水平的突变线粒体DNA（mtDNA）会导致细胞色素c氧化酶（COX）（复合体IV活性）缺乏，因为其13个亚基中的3个由mtDNA编码。相比之下，琥珀酸脱氢酶（SDH）（复合体II活性）保持完整，因为其所有亚基都由核基因编码。在原发性mtDNA疾病和正常衰老肌肉中，含有高水平mtDNA突变的细胞的组织学特征是存在COX缺乏而SDH阳性的细胞。
作者对17例AD患者和17例年龄匹配的对照者的大脑海马切片应用了COX和SDH的连续组织化学方法。这具有既能在原位观察单个细胞，又能测量实际线粒体复合体活性而非仅仅复合体数量的优点。
COX缺乏而SDH阳性的海马神经元和脉络膜上皮细胞在AD患者中比在对照者中更普遍。此外，COX缺乏而SDH阳性的脉络膜细胞与细胞大小增大有关。
COX缺乏而SDH阳性的海马锥体细胞和脉络膜上皮细胞数量增加，有力地证明了在AD中单个细胞中线粒体酶活性缺陷比正常衰老更频繁地发生，并且线粒体可能在AD的发病机制中起重要作用。
