The cholinergic deficit coincides with Aβ deposition at the earliest histopathologic stages of Alzheimer disease
The cholinergic deficit coincides with Aβ deposition at the earliest histopathologic stages of Alzheimer disease
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DOI：
10.1093/jnen/59.4.308
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发表时间：
2000-04-01
影响因子：
3.2
通讯作者：
Roher, AE
中科院分区：
文献类型：
--
作者：
Beach, TG;Kuo, YM;Roher, AE
有效的治疗干预阿尔茨海默病（AD）将是最有效的，如果它是针对早期事件的致病序列。胆碱能缺乏可能是这样一个早期事件。在本研究中，在尸检时检查了26例无认知丧失史且处于AD早期组织病理学阶段（平均Braak分期小于II）的受试者的大脑，以确定皮质胆碱能减少是否与A β浓度或沉积相关。在上级额回和颞下回，含斑块病例的胆碱乙酰转移酶（ChAT）活性显著降低（p < 0.05，非配对双尾t检验），相对于无斑块病例，分别测量为70.9%和79.5%。在颞下回，斯皮尔曼等级相关分析显示，ChAT活性与A β浓度呈显著负相关（p = 0.075; r = -0.3552）。结果表明，胆碱能缺陷是建立在AD的早期组织病理学阶段，在临床症状发作之前。
Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with A beta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with A beta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.