LOSS OF NERVE GROWTH-FACTOR RECEPTOR-CONTAINING NEURONS IN ALZHEIMERS-DISEASE - A QUANTITATIVE-ANALYSIS ACROSS SUBREGIONS OF THE BASAL FOREBRAIN
LOSS OF NERVE GROWTH-FACTOR RECEPTOR-CONTAINING NEURONS IN ALZHEIMERS-DISEASE - A QUANTITATIVE-ANALYSIS ACROSS SUBREGIONS OF THE BASAL FOREBRAIN
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DOI：
10.1016/0014-4886(89)90124-6
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发表时间：
1989-09-01
影响因子：
5.3
通讯作者：
KORDOWER, JH
中科院分区：
文献类型：
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作者：
MUFSON, EJ;BOTHWELL, M;KORDOWER, JH
大细胞神经元包括Ch 1-Ch 4区域的基底前脑提供地形胆碱能神经支配的大脑皮层，丘脑，和基底外侧核的杏仁核。大多数定量研究分析这些神经元在阿尔茨海默氏病（AD）的状态，采用尼斯染色的准备。这些研究主要分析预先指定细胞直径的大神经元。由于基底前脑神经元在阿尔茨海默氏病中萎缩，这些神经元的免疫细胞化学标记物似乎是确定基底前脑亚区中胆碱能神经元是否存在区域特异性变性的更好选择。用抗神经生长因子（NGF）受体的单克隆抗体对7名AD患者和5名年龄匹配的对照患者的脑切片进行免疫细胞化学染色，神经生长因子（NGF）受体是一种探针，先前已证明其与人类胆碱能基底前脑神经元广泛且专门共定位（17，25，35）。与对照组相比，AD组内侧隔（Ch 1）和斜角带（Ch 2）垂直分支的海马投射核内的NGF受体免疫反应阳性神经元受到的影响最小。相比之下，Ch 4区域显示出AD中NGF受体免疫反应性神经元的显著损失，其与疾病过程的持续时间呈负相关（-0.786）。AD患者Ch 4的四个亚区均受到影响，其中前外侧区（76.4%）、中间区（62.1%）和后区（76.5%）的NGF受体免疫反应阳性神经元减少最多。Nissl复染切片未能揭示对NGF受体无免疫反应性的大细胞神经元，这表明免疫细胞化学染色的神经元减少反映了神经元损失，而不是活神经元合成NGF受体的失败。这些数据表明，胆碱能基底前脑神经元的项目杏仁核，以及颞，额基底，额背皮质，在AD的影响最大。
Magnocellular neurons comprising the Ch1-Ch4 regions of the basal forebrain provide topographic cholinergic innervation to the cerebral cortex, thalamus, and basolateral nucleus of the amygdala. Most quantitative studies analyzing the status of these neurons in Alzheimer''s disease (AD) have employed Nissl-stained preparations. These studies principally analyzed large neurons of a prespecified cell diameter. Since basal forebrain neurons atrophy in Alzheimer''s disease, an immunocytochemical marker for these neurons would appear to be a better alternative for determining whether there is regionally specific degeneration of cholinergic neruons across subregions of the basal forebrain. Brain sections from seven AD and five aged-matched control patients were immunocytochemically stained with a monoclonal antibody raised against the receptor for nerve growth factor (NGF), a probe which has previously been demonstrated to extensively and exclusively colocalize with cholinergic basal forebrain neurons in humans (17, 25, 35). NGF receptor-immunoreactive neurons within the hippocampal projecting nuclei of the medial septum (Ch1) and vertical limb of the diagonal band (Ch2) were minimally affected in AD as compared to control cases. In contrast, the Ch4 region demonstrated a significant loss of NGF receptor-immunoreactive neurons in AD that inversely correlated (-0.786) with the duration of the disease process. All four subregions of Ch4 were affected in the AD cases with the anterolateral (76.4%), intermediate (62.1%) and posterior divisions (76.5%) demonstrating the greatest reduction in NGF receptor-immunoreactive neurons. Nissl-counterstained sections failed to reveal magnocellular neurons which were not immunoreactive for the NGF receptor, suggesting that reductions in immunocytochemically stained neurons reflects neuron loss and not the failure of viable neurons to synthesize NGF receptors. These data indicate that cholinergic basal forebrain neurons which project to the amygdala, as well as to the temporal, frontobasal, and frontodorsal cortices, are most affected in AD.