Abstract：
BACKGROUND: Alzheimer\'s disease (AD) is a progressive neurodegenerative illness that leads to impairment of cognitive functions and memory loss. Even though there is a plethora of research reporting the abnormal regulation of VEGF expression in AD pathogenesis, whether the CSF and serum VEGF are increased in AD is an open question yet. In this study, the association of CSF and serum VEGF concentrations with the risk of Alzheimer\'s disease was investigated using systematic review and meta-analysis.
METHODS: A systematic literature search was carried out using online specialized biomedical databases of Web of Science, Pubmed, Scopus, Embase, and Google Scholar until Feb 2023 without restriction to the beginning time. The meta-analysis was performed using the random-effects model and only case-control publications describing VEGF concentrations in Alzheimer\'s patients were considered for calculating the pooled effect size.
RESULTS: In the systematic literature search, 6 and 13 studies met the inclusion criteria to evaluate CSF and serum VEGF concentrations of Alzheimer\'s patients, respectively. This meta-analysis retrieved a total number of 2380 Alzheimer\'s patients and 5368 healthy controls. Under the random-effects model in the meta-analysis, the pooled SMD for CSF and serum VEGF concentrations of Alzheimer\'s patients were -0.13 (95%CI,-0.42-0.16) and 0.23 (95%CI,-0.27-0.73), respectively. Results of meta-regression analysis showed that the quality scores of papers and female sex ratios of participants did not affect the associations of VEGF concentrations with the risk of Alzheimer\'s disease. However, the age average of patients significantly affects the associations of CSF VEGF concentrations with the risk of Alzheimer\'s disease (P=0.051). There was a statistically significant subgroup effect for the disease severity of Alzheimer\'s patients which modifies the associations of serum VEGF concentrations with the risk of Alzheimer\'s disease (P<0.01) and subgroup analysis shows that study location modifies the associations of CSF and serum VEGF concentrations with the risk of Alzheimer\'s disease (P<0.01).
CONCLUSIONS: The results show that the serum VEGF concentrations increased for Alzheimer\'s patients in accordance with the increased expression of VEGF and the VEGF levels of Alzheimer\'s patients decreased by increasing their disease severities. Therefore, in addition to detecting AD in the earliest stages of the disease, serum VEGF could be a promising biomarker to follow up on the disease and evaluate the clinical course of the disease.
METHODS: A systematic literature search was carried out using online specialized biomedical databases of Web of Science, Pubmed, Scopus, Embase, and Google Scholar until Feb 2023 without restriction to the beginning time. The meta-analysis was performed using the random-effects model and only case-control publications describing VEGF concentrations in Alzheimer\'s patients were considered for calculating the pooled effect size.
RESULTS: In the systematic literature search, 6 and 13 studies met the inclusion criteria to evaluate CSF and serum VEGF concentrations of Alzheimer\'s patients, respectively. This meta-analysis retrieved a total number of 2380 Alzheimer\'s patients and 5368 healthy controls. Under the random-effects model in the meta-analysis, the pooled SMD for CSF and serum VEGF concentrations of Alzheimer\'s patients were -0.13 (95%CI,-0.42-0.16) and 0.23 (95%CI,-0.27-0.73), respectively. Results of meta-regression analysis showed that the quality scores of papers and female sex ratios of participants did not affect the associations of VEGF concentrations with the risk of Alzheimer\'s disease. However, the age average of patients significantly affects the associations of CSF VEGF concentrations with the risk of Alzheimer\'s disease (P=0.051). There was a statistically significant subgroup effect for the disease severity of Alzheimer\'s patients which modifies the associations of serum VEGF concentrations with the risk of Alzheimer\'s disease (P<0.01) and subgroup analysis shows that study location modifies the associations of CSF and serum VEGF concentrations with the risk of Alzheimer\'s disease (P<0.01).
CONCLUSIONS: The results show that the serum VEGF concentrations increased for Alzheimer\'s patients in accordance with the increased expression of VEGF and the VEGF levels of Alzheimer\'s patients decreased by increasing their disease severities. Therefore, in addition to detecting AD in the earliest stages of the disease, serum VEGF could be a promising biomarker to follow up on the disease and evaluate the clinical course of the disease.
摘要：
背景：阿尔茨海默病（AD）是一种进行性神经退行性疾病，可导致认知功能受损和记忆丧失。尽管有大量的研究报道VEGF表达在AD发病机制中的异常调控,CSF和血清VEGF是否在AD中增加是一个悬而未决的问题。在这项研究中,采用系统评价和荟萃分析研究了CSF和血清VEGF浓度与阿尔茨海默病风险的相关性.
方法：使用WebofScience的在线专业生物医学数据库进行了系统的文献检索，Pubmed,Scopus,Embase,和谷歌学者，直到2023年2月，没有限制的开始时间。使用随机效应模型进行荟萃分析，仅考虑描述阿尔茨海默病患者VEGF浓度的病例对照出版物来计算合并效应大小。
结果：在系统的文献检索中，6和13项研究符合纳入标准，以评估阿尔茨海默病患者的CSF和血清VEGF浓度，分别。这项荟萃分析共检索到2380名阿尔茨海默氏症患者和5368名健康对照。在荟萃分析的随机效应模型下，阿尔茨海默病患者的CSF和血清VEGF浓度的合并SMD分别为-0.13（95CI，-0.42-0.16）和0.23（95CI，-0.27-0.73），分别。荟萃回归分析结果显示，研究对象的论文质量分数和女性性别比例并不影响VEGF浓度与阿尔茨海默病风险的关系。然而,患者的平均年龄显著影响CSFVEGF浓度与阿尔茨海默病风险的相关性(P=0.051).对阿尔茨海默病患者的疾病严重程度有统计学意义的亚组效应，这改变了血清VEGF浓度与阿尔茨海默病风险的相关性（P<0.01），亚组分析表明，研究位置改变了CSF和血清VEGF浓度与阿尔茨海默病风险的相关性（P<0.01）。
结论：结果表明，阿尔茨海默病患者血清VEGF浓度随着VEGF表达的增加而增加，而阿尔茨海默病患者的VEGF水平随着疾病严重程度的增加而降低。因此,除了在疾病的早期阶段检测AD，血清VEGF可能是一个有希望的生物标志物，用于随访疾病和评估疾病的临床过程。
方法：使用WebofScience的在线专业生物医学数据库进行了系统的文献检索，Pubmed,Scopus,Embase,和谷歌学者，直到2023年2月，没有限制的开始时间。使用随机效应模型进行荟萃分析，仅考虑描述阿尔茨海默病患者VEGF浓度的病例对照出版物来计算合并效应大小。
结果：在系统的文献检索中，6和13项研究符合纳入标准，以评估阿尔茨海默病患者的CSF和血清VEGF浓度，分别。这项荟萃分析共检索到2380名阿尔茨海默氏症患者和5368名健康对照。在荟萃分析的随机效应模型下，阿尔茨海默病患者的CSF和血清VEGF浓度的合并SMD分别为-0.13（95CI，-0.42-0.16）和0.23（95CI，-0.27-0.73），分别。荟萃回归分析结果显示，研究对象的论文质量分数和女性性别比例并不影响VEGF浓度与阿尔茨海默病风险的关系。然而,患者的平均年龄显著影响CSFVEGF浓度与阿尔茨海默病风险的相关性(P=0.051).对阿尔茨海默病患者的疾病严重程度有统计学意义的亚组效应，这改变了血清VEGF浓度与阿尔茨海默病风险的相关性（P<0.01），亚组分析表明，研究位置改变了CSF和血清VEGF浓度与阿尔茨海默病风险的相关性（P<0.01）。
结论：结果表明，阿尔茨海默病患者血清VEGF浓度随着VEGF表达的增加而增加，而阿尔茨海默病患者的VEGF水平随着疾病严重程度的增加而降低。因此,除了在疾病的早期阶段检测AD，血清VEGF可能是一个有希望的生物标志物，用于随访疾病和评估疾病的临床过程。
