Mufson E J, Presley L N, Kordower J H
Christopher Center for Parkinson's Research, Institute for Biogerontology Research, Sun City, AZ 85372.
Brain Res. 1991 Jan 18;539(1):19-30. doi: 10.1016/0006-8993(91)90682-l.
In a effort to better define the role cholinergic basal forebrain neurons play in human cognitive processes, a quantitative assessment of cholinergic nucleus basalis (Ch4) neurons was carried out in 5 patients with Parkinson's disease (PD; 4 non-demented and 1 demented) and 4 age-matched controls using nerve growth factor (NGF) receptor immunohistochemistry as a direct marker for cholinergic basal forebrain neurons. Virtually all (greater than 90%) NGF receptor-containing neurons co-localize with the specific cholinergic marker choline acetyltransferase (ChAT) within the nucleus basalis in PD. NGF receptor-containing neurons were reduced on average by 68% (range 38.6-87.4%) in the non-demented PD cases and by 88.6% in the demented PD patient. Loss of these neurons was heterogeneous across the nucleus basalis subfields with only the anterolateral and posterior Ch4 subregions demonstrating significant reductions of NGF receptor-containing neurons. The reduction in NGF receptor-containing neurons was accompanied by a decrease of acetylcholinesterase (AChE) containing fibers within temporal cortex and in some cases ChAT immunoreactivity in the basolateral amygdaloid nucleus. The numerous non-cholinergic AChE-rich pyramidal cells which were observed throughout the cortex of aged controls were also virtually absent in PD. Although PD patients exhibited severe reductions in Ch4 neurons, few neuritic plaques or neurofibrillary tangles were observed within the PD cortex or Ch4 and similar numbers of these AD-type pathologies were seen within age-matched controls. This suggests that Ch4 degeneration alone is not sufficient to induce such cytoskeletal abnormalities and that the neuron loss seen within Ch4 in AD and PD may be mediated through different processes. These results, coupled with the extensive basic and clinical literature linking acetylcholine and memory function, further indicate that Ch4 degeneration without additional cortical and/or subcortical pathology is not sufficient to impair cognition in PD. Perhaps additional pathology must be superimposed upon nucleus basalis degeneration to induce dementia in humans.
为了更好地确定胆碱能基底前脑神经元在人类认知过程中所起的作用，我们使用神经生长因子（NGF）受体免疫组织化学作为胆碱能基底前脑神经元的直接标记物，对5例帕金森病（PD；4例非痴呆和1例痴呆）患者和4例年龄匹配的对照者的胆碱能基底核（Ch4）神经元进行了定量评估。在PD患者的基底核内，几乎所有（超过90%）含NGF受体的神经元都与特异性胆碱能标记物胆碱乙酰转移酶（ChAT）共定位。在非痴呆的PD病例中，含NGF受体的神经元平均减少了68%（范围为38.6 - 87.4%），在痴呆的PD患者中减少了88.6%。这些神经元的丧失在基底核亚区域是不均匀的，只有前外侧和后Ch4亚区域显示含NGF受体的神经元有显著减少。含NGF受体的神经元减少伴随着颞叶皮质内乙酰胆碱酯酶（AChE）阳性纤维的减少，在某些情况下，基底外侧杏仁核内的ChAT免疫反应性也降低。在老年对照者的整个皮质中观察到的大量富含非胆碱能AChE的锥体细胞在PD患者中也几乎不存在。尽管PD患者的Ch4神经元严重减少，但在PD皮质或Ch4内几乎未观察到神经炎性斑块或神经原纤维缠结，在年龄匹配的对照者中也观察到了类似数量的这些AD型病理改变。这表明仅Ch4变性不足以诱导这种细胞骨架异常，并且在AD和PD中Ch4内所见的神经元丧失可能通过不同的过程介导。这些结果，再加上将乙酰胆碱与记忆功能联系起来的大量基础和临床文献，进一步表明没有额外皮质和/或皮质下病变的Ch4变性不足以损害PD患者的认知。也许必须在基底核变性的基础上叠加额外的病变才能导致人类痴呆。
