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Cerebrospinal Fluid and Serum d-Serine Levels in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

by 1,2,3, 3,4, 4,5,6 and 7,8,*
1
Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan
2
Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan
3
An Nan Hospital, China Medical University, Tainan 709204, Taiwan
4
School of Nursing, China Medical University, Taichung 40402, Taiwan
5
Ph.D Program for Health Science and Industry, China Medical University, Taichung 40402, Taiwan
6
Adjunct Supervisor, Department of Nursing, China Medical University Hospital, Taichung 40402, Taiwan
7
Department of Psychiatry, Tzu-Chi General Hospital, Hualien 970473, Taiwan
8
Institute of Medical Sciences, Tzu Chi University, Hualien 970473, Taiwan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(12), 3840; https://doi.org/10.3390/jcm9123840
Received: 13 October 2020 / Revised: 23 November 2020 / Accepted: 24 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
Objective: 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. Methods: 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 I2 statistic. Moderators of effects were explored using metaregression. Results: 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, p < 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, p = 0.0004). Conclusions: 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. View Full-Text
Keywords: d-serine; Alzheimer’s disease d-serine; Alzheimer’s disease
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MDPI and ACS Style

Chang, C.-H.; Kuo, H.-L.; Ma, W.-F.; Tsai, H.-C. Cerebrospinal Fluid and Serum d-Serine Levels in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J. Clin. Med. 2020, 9, 3840. https://doi.org/10.3390/jcm9123840

AMA Style

Chang C-H, Kuo H-L, Ma W-F, Tsai H-C. Cerebrospinal Fluid and Serum d-Serine Levels in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2020; 9(12):3840. https://doi.org/10.3390/jcm9123840

Chicago/Turabian Style

Chang, Chun-Hung, Hsiao-Lun Kuo, Wei-Fen Ma, and Hsin-Chi Tsai. 2020. "Cerebrospinal Fluid and Serum d-Serine Levels in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis" Journal of Clinical Medicine 9, no. 12: 3840. https://doi.org/10.3390/jcm9123840

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