Procter A W, Palmer A M, Francis P T, Lowe S L, Neary D, Murphy E, Doshi R, Bowen D M
Institute of Neurology, London, England.
J Neurochem. 1988 Mar;50(3):790-802. doi: 10.1111/j.1471-4159.1988.tb02983.x.
Excitatory dicarboxylic amino acids previously have been ascribed several functions in the brain. Here their total concentration and proposed neurochemical markers of neurotransmitter function have been measured in brain from patients with Alzheimer's disease (AD) and controls. Specimens were obtained antemortem (biopsy) approximately 3 years after emergence of symptoms and promptly (less than 3 h) postmortem some 10 years after onset. Early in the disease a slight elevation in aspartic acid concentration of cerebral cortex was observed in the patients with AD. A reduction in glutamic acid concentration of a similar magnitude was found. It is argued that this, together with a decrease in CSF glutamine content and lack of change in the phosphate-activated brain glutaminase activity of tissue, reflects an early metabolic abnormality. Later in the disease evidence of glutamatergic neurone loss is provided by the finding that in many regions of the cerebral cortex the Na+-dependent uptake of D-[3H]aspartic acid was almost always lowest in AD subjects compared with control when assessed by a method designed to minimise artifacts and epiphenomena. Release of endogenous neurotransmitters from human brain tissue postmortem did not appear to have the characteristics of that from human tissue antemortem and rat brain.
兴奋性二羧酸氨基酸此前已被认为在大脑中具有多种功能。在此，我们测定了阿尔茨海默病（AD）患者和对照组大脑中它们的总浓度以及推测的神经递质功能的神经化学标志物。标本在症状出现后约3年进行生前获取（活检），并在发病后约10年迅速（少于3小时）进行死后获取。在疾病早期，AD患者大脑皮质中天冬氨酸浓度略有升高。同时发现谷氨酸浓度有类似程度的降低。有人认为，这与脑脊液谷氨酰胺含量的降低以及组织中磷酸激活脑谷氨酰胺酶活性缺乏变化一起，反映了早期代谢异常。在疾病后期，通过一种旨在尽量减少假象和附带现象的方法评估发现，与对照组相比，AD患者大脑皮质许多区域中依赖钠的D-[3H]天冬氨酸摄取几乎总是最低的，这为谷氨酸能神经元丢失提供了证据。死后从人脑组织释放内源性神经递质似乎不具有生前人体组织和大鼠脑组织释放神经递质的特征。
