Sayre L M, Zelasko D A, Harris P L, Perry G, Salomon R G, Smith M A
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, U.S.A.
J Neurochem. 1997 May;68(5):2092-7. doi: 10.1046/j.1471-4159.1997.68052092.x.
Recent studies have demonstrated oxidative damage is one of the salient features of Alzheimer's disease (AD). In these studies, glycoxidation adduction to and direct oxidation of amino acid side chains have been demonstrated in the lesions and neurons of AD. To address whether lipid damage may also play an important pathogenic role, we raised rabbit antisera specific for the lysine-derived pyrrole adducts formed by lipid peroxidation-derived 4-hydroxynonenal (HNE). These antibodies were used in immunocytochemical evaluation of brain tissue from AD and age-matched control patients. HNE-pyrrole immunoreactivity not only was identified in about half of all neurofibrillary tangles, but was also evident in neurons lacking neurofibrillary tangles in the AD cases. In contrast, few senile plaques were labeled, and then only the dystrophic neurites were weakly stained, whereas the amyloid-beta deposits were unlabeled. Age-matched controls showed only background HNE-pyrrole immunoreactivity in hippocampal or cortical neurons. In addition to providing further evidence that oxidative stress-related protein modification is a pervasive factor in AD, the known neurotoxicity of HNE suggests that lipid peroxidation may also play a role in the neuronal death in AD that underlies cognitive deficits.
最近的研究表明，氧化损伤是阿尔茨海默病（AD）的显著特征之一。在这些研究中，已在AD的病变和神经元中证实了糖氧化加成以及氨基酸侧链的直接氧化。为了探究脂质损伤是否也可能发挥重要的致病作用，我们制备了针对脂质过氧化衍生的4-羟基壬烯醛（HNE）形成的赖氨酸衍生吡咯加合物的兔抗血清。这些抗体用于对AD患者和年龄匹配的对照患者的脑组织进行免疫细胞化学评估。HNE-吡咯免疫反应性不仅在所有神经原纤维缠结的约一半中被识别，而且在AD病例中缺乏神经原纤维缠结的神经元中也很明显。相比之下，很少有老年斑被标记，而且只有营养不良的神经突被弱染色，而淀粉样β沉积物未被标记。年龄匹配的对照组在海马或皮质神经元中仅显示背景HNE-吡咯免疫反应性。除了进一步证明氧化应激相关的蛋白质修饰是AD中的一个普遍因素外，HNE已知的神经毒性表明脂质过氧化也可能在AD中导致认知缺陷的神经元死亡中起作用。
