Regional decreases of free D-aspartate levels in Alzheimer's disease
Regional decreases of free D-aspartate levels in Alzheimer's disease
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DOI：
10.1016/s0304-3940(98)00451-0
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发表时间：
1998-07-03
影响因子：
2.5
通讯作者：
Di Fiore, MM
中科院分区：
文献类型：
--
作者：
D'Aniello, A;Lee, JM;Di Fiore, MM
N-甲基-D-天冬氨酸 (NMDA) 受体已被证明参与学习和记忆过程。在阿尔茨海默病中，NMDA 受体减少。由于 D-天冬氨酸是 NMDA 受体的内源性激动剂，我们假设，如果阿尔茨海默病患者大脑中这种氨基酸的水平降低，可能会导致 NMDA 受体信号转导系统的减少，并导致这些患者出现明显的记忆缺陷。因此，使用色谱 HPLC 方法，确定了阿尔茨海默病 (AD) 患者 (n = 5) 和年龄匹配对照 (n = 5) 死后人脑样本中游离 D-天冬氨酸水平的区域分布。我们发现，与对照组相比，阿尔茨海默病患者的 D-天冬氨酸水平显着降低（范围：-35% 至 -47%；P < 0.01）。然而，在小脑中没有发现任何差异，小脑是一个不受 AD 神经病理变化影响的区域。这些数据表明，D-天冬氨酸水平降低可能导致 NMDA 受体功能降低，从而导致 AD (C) 1998 Elsevier Science Ireland Ltd. 中所见的记忆缺陷。保留所有权利。
N-methyl-D-aspartate (NMDA) receptors have been shown to be involved in learning and memory processes. In Alzheimer's disease, there is a reduction of NMDA receptors. Since D-aspartate is an endogenous agonist for the NMDA receptor, we hypothesised that if there are reduced levels of this amino acid in the Alzheimer's brain, this could raise the reduction of NMDA receptor signal transduction system and contribute to the marked memory deficits seen in these patients. Therefore, using a chromatographic HPLC method, the regional distribution of free D-aspartate levels in post-mortem human brain samples from patients with Alzheimer's disease (AD) (n = 5) and age-matched controls (n = 5) were determined. We found that the levels of D-aspartate are significantly lower in Alzheimer's patients compared to controls (range: from -35 to -47%; P < 0.01). However, no differences were found in the cerebellum, a region spared from the neuropathological changes of AD. These data suggest that decreased levels of D-aspartate could contribute to a lower NMDA receptor function and consequently contribute to the memory deficits seen in AD (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.