Bowen D M, Smith C B, White P, Davison A N
Brain. 1976 Sep;99(3):459-96. doi: 10.1093/brain/99.3.459.
Fifty-six brains from middle-aged and elderly normal as well as demented subjects and patients with provisional clinical diagnosis of other neurological and psychiatric diseases were assessed histologically. On this basis the specimens were classified into 14 diagnostic groups. A survey of potential indices of specific neurons has been carried out on these brains in which neurotransmitter-related enzymes, gamma-GTP (a potential index of capillaries) and specific proteins have been determined in up to 20 brain regions. In addition, the agonal state has been tentatively assessed by examining the post-mortem states of the circulatory and respiratory systems. CAT and gamma-GTP activities and the concentration of a soluble neuronal-type protein (neuronin S-5) were found to be relatively unaffected by the agonal state. When cases of senile dementia were compared to controls (matched with respect to the cause of death) the activity of CAT (the potential index of cholinergic neurons) appears to be reduced in the cerebral cortex. This is a preliminary finding, although a correlation was indicated between CAT activity and 'senile' morphological changes, the activity was markedly reduced in only 3 brains. However, despite inconsistencies in the literature (Karczmar, 1975) at least one pharmacological study on humans appears to show that the cholinergic system may be involved in age-related memory degeneration (Drachman and Leavitt, 1974). Cholinergic neurons may be abnormal in the other abiotrophies examined (Huntington's chorea, motor neuron disease and mixed vascular and senile dementia). gamma-GTP and neuronin S-5 (identical in most respects to the soluble acidic neuronal protein 14-3-2 of antigen alpha) were not reduced in senile dementia. The activities of brain decarboxylase (GAD and AAD) and the concentration of another soluble acidic brain protein (neuronin S-6) appear to be affected by the agonal state. This is remarkable because GAD and, in particular, neuronin S6, are relatively unaffected by post-mortem autolysis. As judged by the state of the extraneural systems which regulated the blood and oxygen supply to the brain it appears that terminal 'cerebral hypoxia' is responsible for the depletion of these brain constituents. This effect appears to be particularly marked in deep grey matter. In non-demented patients that die of bronchopneumonia, the areas of the cortex which are depleted in neuronin S-6 are consistent with the pattern of the 'selective vulnerability' of the cortex to hypoxia, suggesting that the terminal state can also affect the neocortex. If so, then this is particularly relevant to studies on senile dementia, for the effect of the terminal bronchopneumonia that so often occurs in these patients (and in patients with other abiotrophies) may be exacerbated by a terminal reduction in cerebral blood flow...
对56例来自中年和老年正常受试者、痴呆患者以及临床初步诊断为其他神经和精神疾病的患者的大脑进行了组织学评估。在此基础上，将标本分为14个诊断组。对这些大脑进行了特定神经元潜在指标的调查，其中在多达20个脑区测定了与神经递质相关的酶、γ-谷氨酰转肽酶（γ-GTP，毛细血管的潜在指标）和特定蛋白质。此外，通过检查循环和呼吸系统的死后状态初步评估了濒死状态。发现过氧化氢酶（CAT）和γ-GTP活性以及一种可溶性神经元型蛋白质（神经素S-5）的浓度相对不受濒死状态的影响。将老年痴呆病例与对照组（在死因方面匹配）进行比较时，发现大脑皮质中CAT（胆碱能神经元的潜在指标）的活性似乎降低。这是一个初步发现，尽管CAT活性与“老年”形态学变化之间存在相关性，但仅在3个大脑中活性明显降低。然而，尽管文献中存在不一致之处（卡尔兹马尔，1975年），但至少一项针对人类的药理学研究似乎表明胆碱能系统可能参与与年龄相关的记忆衰退（德拉赫曼和利维特，1974年）。在所检查的其他营养缺乏症（亨廷顿舞蹈病、运动神经元病以及混合性血管性和老年性痴呆）中，胆碱能神经元可能存在异常。老年痴呆患者的γ-GTP和神经素S-5（在大多数方面与抗原α的可溶性酸性神经元蛋白14-3-2相同）并未降低。脑脱羧酶（谷氨酸脱羧酶和天冬氨酸脱羧酶）的活性以及另一种可溶性酸性脑蛋白（神经素S-6）的浓度似乎受濒死状态的影响。这很显著，因为谷氨酸脱羧酶，特别是神经素S6，相对不受死后自溶的影响。从调节大脑血液和氧气供应的神经外系统状态判断，似乎终末期“脑缺氧”是这些脑成分消耗的原因。这种影响在深部灰质中似乎尤为明显。在死于支气管肺炎的非痴呆患者中，神经素S-6耗尽的皮质区域与皮质对缺氧的“选择性易损性”模式一致，这表明终末期状态也会影响新皮质。如果是这样，那么这对于老年性痴呆的研究尤为重要，因为这些患者（以及其他营养缺乏症患者）中经常发生的终末期支气管肺炎的影响可能会因脑血流量的终末期减少而加剧……
