Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Sci Rep. 2017 Nov 1;7(1):14849. doi: 10.1038/s41598-017-13951-7.
Feasible peripheral biomarker for Alzheimer's disease (AD) is lacking. Dysregulation of N-methyl-D-aspartate (NMDA) receptor is implicated in the pathogenesis of AD. D-amino acid oxidase (DAO) and amino acids can regulate the NMDA receptor function. This study aimed to examine whether peripheral DAO and amino acids levels are characteristic of age-related cognitive decline. We enrolled 397 individuals (including amnestic mild cognitive impairment (MCI), mild AD, moderate to severe AD, and healthy elderly). DAO levels in the serum were measured using ELISA. Amino acids levels in serum were measured by high performance liquid chromatography. Severity of the cognitive deficits in subjects was assessed using Clinical Dementia Rating Scale (CDR). The DAO levels increased with the severity of the cognitive deficits. DAO levels were significantly associated with D-glutamate and D-serine levels. The Receiver Operating Characteristics analysis of DAO levels for AD patients vs. healthy controls determined the optimal cutoff value, 30.10, with high sensitivity (0.842) and specificity (0.889) (area under curve = 0.928). This is the first study indicating that the peripheral DAO levels may increase with age-related cognitive decline. The finding supports the hypofunction of NMDA receptor hypothesis in AD. Whether DAO could serve as a potential surrogate biomarker needs further studies.
目前缺乏阿尔茨海默病（AD）的可行外周生物标志物。N-甲基-D-天冬氨酸（NMDA）受体的失调与 AD 的发病机制有关。D-氨基酸氧化酶（DAO）和氨基酸可以调节 NMDA 受体功能。本研究旨在探讨外周 DAO 和氨基酸水平是否与年龄相关的认知能力下降有关。我们纳入了 397 名个体（包括遗忘型轻度认知障碍（MCI）、轻度 AD、中度至重度 AD 和健康老年人）。使用 ELISA 测定血清中的 DAO 水平。通过高效液相色谱法测定血清中氨基酸水平。使用临床痴呆评定量表（CDR）评估受试者认知缺陷的严重程度。DAO 水平随认知缺陷的严重程度而升高。DAO 水平与 D-谷氨酸和 D-丝氨酸水平显著相关。DAO 水平对 AD 患者与健康对照组的受试者工作特征分析确定了最佳截断值为 30.10，具有较高的敏感性（0.842）和特异性（0.889）（曲线下面积= 0.928）。这是第一项表明外周 DAO 水平可能随年龄相关的认知能力下降而升高的研究。这一发现支持 NMDA 受体功能低下假说在 AD 中的作用。DAO 是否可以作为潜在的替代生物标志物需要进一步研究。
