Chang Chun-Hung, Kuo Hsiao-Lun, Ma Wei-Fen, Tsai Hsin-Chi
Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan.
Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan.
J Clin Med. 2020 Nov 26;9(12):3840. doi: 10.3390/jcm9123840.
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor coagonist, is reported as a potential new biomarker for AD. However, the results of serum and cerebrospinal fluid (CSF) d-serine levels are conflicting. We conducted a meta-analysis to investigate the serum and CSF d-serine levels in patients with AD.
We searched PubMed, the Cochrane central register of controlled trials, and the Cochrane database of systematic reviews for trials that measured d-serine levels both in patients with AD and in controls. We included controlled trials that analyzed d-serine levels in human samples (e.g., serum and CSF). Studies were pooled using a random-effect model for comparisons between AD and control group. We used effect size (ES; expressed as d-serine levels) in each selected meta-analysis to calculate standardized mean difference (SMD). Positive values indicated increased d-serine levels in AD group. We presented results with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visually inspecting funnel plots and using the I statistic. Moderators of effects were explored using metaregression.
Seven trials with more than 1186 participants were included in this meta-analysis. d-serine levels in patients with AD were significantly higher than those in controls (SMD = 0.679, 95% CI = 0.335 to 1.022, < 0.001). Subgroup analyses showed that the AD group had significantly higher d-serine levels in serum and CSF compared with the control group (SMD = 0.566 (serum) and 1.008 (CSF); 95% CI = 0.183 to 0.948 (serum) and 0.168 to 1.849 (CSF)). Moreover, a metaregression revealed a significant negative association between ES and mean mini-mental state examination score in AD group (slope = -0.1203, = 0.0004).
Our results revealed higher d-serine levels in the serum and CSF of patients with AD relative to the controls. Further studies with a larger sample size and longer follow-up are recommended to clarify this association.
阿尔茨海默病（AD）是一种复杂且严重的神经退行性疾病，目前仍缺乏有效的诊断方法。已发现N-甲基-D-天冬氨酸受体（NMDAR）功能障碍与AD机制中的突触功能障碍和神经毒性有关。D-丝氨酸作为一种NMDAR受体协同激动剂，被报道为AD潜在的新型生物标志物。然而，血清和脑脊液（CSF）中D-丝氨酸水平的研究结果存在矛盾。我们进行了一项荟萃分析，以研究AD患者血清和脑脊液中D-丝氨酸水平。
我们检索了PubMed、Cochrane对照试验中心注册库和Cochrane系统评价数据库，查找测量AD患者和对照组D-丝氨酸水平的试验。我们纳入了分析人类样本（如血清和脑脊液）中D-丝氨酸水平的对照试验。采用随机效应模型对AD组和对照组进行比较并汇总研究。在每项选定的荟萃分析中，我们使用效应量（ES；以D-丝氨酸水平表示）来计算标准化平均差（SMD）。正值表示AD组D-丝氨酸水平升高。我们给出了95%置信区间（CI）的结果。通过直观检查漏斗图和使用I统计量评估纳入试验的异质性。使用元回归探索效应调节因素。
本荟萃分析纳入了7项试验，涉及1186多名参与者。AD患者的D-丝氨酸水平显著高于对照组（SMD = 0.679，95%CI = 0.335至1.022，P < 0.001）。亚组分析显示，与对照组相比，AD组血清和脑脊液中的D-丝氨酸水平显著更高（SMD = 0.566（血清）和1.008（脑脊液）；95%CI = 0.183至0.948（血清）和0.168至1.849（脑脊液））。此外，元回归显示AD组中ES与简易精神状态检查平均得分之间存在显著负相关（斜率 = - ）。
我们的结果显示，与对照组相比，AD患者血清和脑脊液中的D-丝氨酸水平更高。建议进行更大样本量和更长随访时间的进一步研究，以阐明这种关联。 0.1203，P = 0.0004）
