Inherent abnormalities in energy metabolism in Alzheimer disease - Interaction with cerebrovascular compromise
Inherent abnormalities in energy metabolism in Alzheimer disease - Interaction with cerebrovascular compromise
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DOI：
10.1111/j.1749-6632.2000.tb06370.x
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Gibson, GE
中科院分区：
文献类型：
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作者：
Blass, JP;Sheu, RKF;Gibson, GE
阿尔茨海默病(AD)是痴呆症的一种形式。AD似乎有多种基本病因，导致定义该疾病的神经病理表现。阿尔茨海默病高危患者通常在神经心理、电生理和神经影像检查中表现出临床疾病的证据之前，就已经在体内表现出脑代谢率的损害。因此，阿尔茨海默病患者能量代谢障碍不能归因于脑实质丢失或电生理异常。在AD大脑的特征异常中，有几种酶复合体缺乏，这些酶复合体参与底物的线粒体氧化产生能量。其中包括丙酮酸脱氢酶复合体(PDHC)、α-酮戊二酸脱氢酶复合体(KGDHC)和电子传递链复合体IV(COX)，KGDHC的缺失可能是由于多种原因造成的，包括自由基的损伤，也可能是编码该复合体核心蛋白的DLST基因的遗传变异。AD大脑固有的葡萄糖氧化损伤可能与AD大脑的氧气和葡萄糖供应受损协同作用，从而导致脑损伤。这些考虑导致了一种假设，即脑血管损害和大脑氧化底物能力的固有异常可以相互作用，有利于在遗传上易患神经性斑块的人中发展为阿尔茨海默病。
Alzheimer disease (AD) is a form of the dementia syndrome. AD appears to have a variety of fundamental etiologies that Lead to the neuropathological manifestations which define the disease. Patients who are at high risk to develop AD typically show impairments of cerebral metabolic rate in vivo even before they show any evidence of the clinical disease on neuropsychologic al, electrophysiological, and neuroimaging examinations. Therefore, impairment in energy metabolism in AD can not be attributed to loss of brain substance or to electrophysiological abnormalities. Among the characteristic abnormalities in the AD brain are deficiencies in several enzyme complexes which participate in the mitochondrial oxidation of substrates to yield energy. These include the pyruvate dehydrogenase complex (PDHC), the alpha-ketoglutarate dehydrogenase complex (KGDHC), and Complex IV of the electron transport chain (COX), The deficiency of KGDHC may be due to a mixture of causes including damage by free radicals and perhaps to genetic variation in the DLST gene encoding the core protein of this complex. Inherent impairment of glucose oxidation by the AD brain may reasonably be expected to interact synergistically with an impaired supply of oxygen and glucose to the AD brain, in causing brain damage. These considerations lead to the hypothesis that cerebrovascular compromise and inherent abnormalities in the brain's ability to oxidize substrates can interact to favor the development of AD, in individuals who are genetically predisposed to develop neuritic plaques.