Bigl M, Bleyl A D, Zedlick D, Arendt T, Bigl V, Eschrich K
Institute of Biochemistry, School of Medicine, University of Leipzig, Germany.
J Neurochem. 1996 Sep;67(3):1164-71. doi: 10.1046/j.1471-4159.1996.67031164.x.
A severe reduction of the in vivo cerebral glucose consumption rate is generally found in patients with Alzheimer's disease. In postmortem studies changes in the activities of key regulatory glycolytic enzymes, including 6-phosphofructokinase (PFK), have been reported in Alzheimer's disease brains, but the results obtained so far are inconsistent and controversial. We reevaluated the activity of PFK in brain tissue from clinically and neuropathologically confirmed cases of Alzheimer's disease using optimized tissue disintegration and assay methods and determined the PFK isozyme pattern. PFK activity in brains from patients with Alzheimer's disease was significantly increased in frontal and temporal cortex and unchanged in the other brain areas studied when compared with control brains. All three PFK isozymes were detected in each of the brain areas studied. In brains of Alzheimer's disease patients the level of the C-type PFK was slightly reduced at the expense of the M- and L-type subunits. The data presented do not support the results of other groups, which reported up to a 90% reduction of PFK activity in Alzheimer's disease. In contrast, the data presented clearly rule out the suggestion that changes of PFK activity might be one of the causes for the reduced glucose consumption in Alzheimer's disease brains.
阿尔茨海默病患者体内脑葡萄糖消耗率通常会大幅降低。在尸检研究中，已有报道称阿尔茨海默病患者大脑中关键调节糖酵解酶的活性发生了变化，包括6-磷酸果糖激酶（PFK），但目前得到的结果并不一致且存在争议。我们使用优化的组织破碎和检测方法，重新评估了临床和神经病理学确诊的阿尔茨海默病病例脑组织中PFK的活性，并确定了PFK同工酶模式。与对照大脑相比，阿尔茨海默病患者大脑额叶和颞叶皮质中的PFK活性显著增加，而在其他研究的脑区中则没有变化。在所研究的每个脑区中都检测到了所有三种PFK同工酶。在阿尔茨海默病患者的大脑中，C型PFK的水平略有降低，而M型和L型亚基的水平则相应升高。本文所呈现的数据不支持其他研究小组的结果，他们报道称阿尔茨海默病中PFK活性降低高达90%。相反，本文所呈现的数据明确排除了PFK活性变化可能是阿尔茨海默病患者大脑葡萄糖消耗减少原因之一的说法。
