Smith C D, Carney J M, Starke-Reed P E, Oliver C N, Stadtman E R, Floyd R A, Markesbery W R
Department of Neurology, University of Kentucky Medical Center, Lexington 40536.
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10540-3. doi: 10.1073/pnas.88.23.10540.
The relationship between Alzheimer disease (AD) and aging is not currently known. In this study, postmortem frontal- and occipital-pole brain samples were obtained from 16 subjects with AD, 8 age-matched controls, and 5 young controls. These samples were analyzed both for protein oxidation products (carbonyl) and the activities of two enzymes vulnerable to mixed-function oxidation, glutamine synthetase and creatine kinase. Glutamine synthetase is more sensitive to mixed-function oxidation than creatine kinase. Carbonyl content rises exponentially with age, at double the rate in the frontal pole compared with the occipital pole. Compared with young controls, both aged groups (AD and age-matched controls) have increased carbonyl content and decreased glutamine synthetase and creatine kinase activities, which are more marked in the frontal than occipital pole in all instances. We conclude that protein oxidation products accumulate in the brain and that oxidation-vulnerable enzyme activities decrease with aging in the same regional pattern (frontal more affected than occipital). However, only glutamine synthetase activity distinguishes AD from age-matched controls: Because glutamine synthetase activity is differentially reduced in the frontal pole in AD, we suggest that AD may represent a specific brain vulnerability to age-related oxidation.
目前尚不清楚阿尔茨海默病（AD）与衰老之间的关系。在本研究中，从16名AD患者、8名年龄匹配的对照者和5名年轻对照者身上获取了死后额叶和枕叶脑样本。对这些样本进行了蛋白质氧化产物（羰基）以及两种易受混合功能氧化影响的酶——谷氨酰胺合成酶和肌酸激酶活性的分析。谷氨酰胺合成酶比肌酸激酶对混合功能氧化更敏感。羰基含量随年龄呈指数增长，额叶的增长速度是枕叶的两倍。与年轻对照者相比，两个老年组（AD患者和年龄匹配的对照者）的羰基含量均增加，谷氨酰胺合成酶和肌酸激酶活性均降低，在所有情况下，额叶的变化均比枕叶更为明显。我们得出结论，蛋白质氧化产物在大脑中积累，且氧化易损酶活性随衰老以相同的区域模式降低（额叶比枕叶受影响更大）。然而，只有谷氨酰胺合成酶活性能够将AD与年龄匹配的对照者区分开来：由于AD患者额叶中的谷氨酰胺合成酶活性有差异地降低，我们认为AD可能代表了大脑对与年龄相关的氧化的一种特定易损性。
