Region-specific neurotrophin imbalances in Alzheimer disease Decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas
Region-specific neurotrophin imbalances in Alzheimer disease Decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas
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DOI：
10.1001/archneur.57.6.846
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发表时间：
2000-06-01
影响因子：
--
通讯作者：
Otten, U
中科院分区：
文献类型：
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作者：
Hock, C;Heese, K;Otten, U
背景：神经生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养素3(NT-3)和神经营养素4/5(NT-4/5)是神经营养素基因家族的成员，它们支持特定神经元群体的生存，包括阿尔茨海默病(AD)神经退行性变(AD)患者。目的：确定AD患者脑内神经营养素蛋白水平是否与对照组相比发生改变。方法：我们对AD患者死后海马、额叶和顶叶皮质、NT-4/5的NGF、BDNF、NT-3和NT-4/5的蛋白水平进行了定量，并计算了神经营养素/NT-3的比值和小脑，并与年龄匹配的对照组进行比较(AD患者/对照组：海马区，9/9例；额叶皮质19/9，顶叶皮质8/5，小脑5/7)。我们在快速尸检衍生的脑组织中应用了高灵敏度和特异性的酶联免疫吸附试验(Mean+/-SD Death Interval，2.57+/-1.75h，n=71)，以最大限度地减少死后蛋白分解活性。
Background: Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5) are members of the neurotrophin gene family that support the survival of specific neuronal populations, including those that are affected by neurodegeneration in Alzheimer disease (AD).Objective: To determine whether neurotrophin protein levels are altered in the AD-affected brain compared with control brains.Methods: We quantitated protein levels of NGF, BDNF, NT-3, and NT-4/5, and calculated neurotrophin/NT-3 ratios in AD-affected postmortem hippocampus, frontal and parietal cortex, and cerebellum, and compared them with age-matched control tissue (patients with AD/controls: hippocampus, 9/9 cases; frontal cortex, 19/9; parietal cortex 8/5; and cerebellum 5/7, respectively). We applied highly sensitive and specific enzyme-linked immunosorbent assays in rapid-autopsy-derived brain tissue (mean+/-SD postmortem interval, 2.57 +/- 1.75 h, n = 71) to minimize postmortem proteolytic activity.Results: Levels of BDNF were significantly reduced in hippocampus and parietal cortex (P