Lowe S L, Francis P T, Procter A W, Palmer A M, Davison A N, Bowen D M
Miriam Marks Department of Neurochemistry, Institute of Neurology, London, UK.
Brain. 1988 Aug;111 ( Pt 4):785-99. doi: 10.1093/brain/111.4.785.
The concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), was measured in the cerebral cortex obtained at diagnostic craniotomy from 10 patients with Alzheimer's disease of 3 yrs mean duration and 6 patients with other causes of dementia, and from 31 subjects undergoing other neurosurgical procedures (for which removal of apparently normal tissue was necessary). GABA content of 5 areas of the cerebral cortex and the cerebellar cortex was measured postmortem in the brains of 23 Alzheimer and 19 control subjects and 5 patients with other causes of dementia. Fourteen of these specimens, including 7 from patients with Alzheimer's disease of 8 yrs mean duration, were obtained within 3 h of death. These were processed in a similar manner to the neurosurgical specimens and are regarded also as fresh tissue samples. The remaining 33 specimens are regarded as conventional postmortem samples as the mean interval of death to autopsy was 21 h. GABA concentration in conventional autopsy specimens from Alzheimer subjects was not reduced as compared with controls in either cingulate or cerebellar cortex. In the inferior parietal cortex, agonal status confounded this comparison. The concentration was reduced in superior parietal, frontal and temporal cortex but there is a possibility that agonal state also confounded these comparisons. There was no deficit in GABA concentration in fresh cortical tissue from Alzheimer patients except for the temporal lobe from autopsy specimens. The content of somatostatin-like immunoreactivity was, like GABA, found to be comparable to control in some groups of Alzheimer specimens. It is argued that the deficits in autopsy samples and lack of change in surgical specimens is likely to be due to the duration of illness at the time of sampling. Losses of choline acetyltransferase activity were observed in all groups of Alzheimer specimens in all areas of brain studied. The data are consistent with other results which suggest that cholinergic under-activity is most closely related to the clinical course of Alzheimer's disease.
在诊断性开颅手术中，从10例平均病程为3年的阿尔茨海默病患者、6例其他原因导致痴呆的患者以及31例接受其他神经外科手术（需要切除看似正常的组织）的受试者获取大脑皮层，测量抑制性神经递质γ-氨基丁酸（GABA）的浓度。在23例阿尔茨海默病患者、19例对照受试者以及5例其他原因导致痴呆的患者死后大脑中，测量大脑皮层和小脑皮层5个区域的GABA含量。其中14个标本，包括7例平均病程为8年的阿尔茨海默病患者的标本，在死亡后3小时内获取。这些标本的处理方式与神经外科标本相似，也被视为新鲜组织样本。其余33个标本被视为常规尸检样本，因为死亡至尸检的平均间隔时间为21小时。与对照组相比，阿尔茨海默病患者常规尸检标本中扣带回或小脑皮层的GABA浓度并未降低。在顶下叶皮层，濒死状态混淆了这种比较。在顶上叶、额叶和颞叶皮层中浓度降低，但濒死状态也有可能混淆了这些比较。除了尸检标本的颞叶外，阿尔茨海默病患者新鲜皮层组织中的GABA浓度没有缺陷。在某些阿尔茨海默病标本组中，发现生长抑素样免疫反应性的含量与对照组相当，与GABA情况相同。有人认为，尸检样本中的缺陷和手术标本中缺乏变化可能是由于取样时的病程长短所致。在所有研究的大脑区域中，所有阿尔茨海默病标本组均观察到胆碱乙酰转移酶活性降低。这些数据与其他结果一致，表明胆碱能活性不足与阿尔茨海默病的临床病程关系最为密切。
