Seyed Salman Zakariaee, Department of Medical Physics, Faculty of Paramedical Sciences, Ilam University of Medical Sciences, Ilam, Iran. Email address:
J Prev Alzheimers Dis. 2024;11(3):721-729. doi: 10.14283/jpad.2024.18.
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.
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.
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).
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.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，可导致认知功能障碍和记忆力减退。尽管有大量研究报告称血管内皮生长因子（VEGF）的表达异常与 AD 发病机制有关，但 CSF 和血清 VEGF 是否在 AD 中增加仍是一个悬而未决的问题。在这项研究中，我们使用系统评价和荟萃分析研究了 CSF 和血清 VEGF 浓度与 AD 风险的关系。
使用在线专门的生物医学数据库 Web of Science、Pubmed、Scopus、Embase 和 Google Scholar 进行系统文献检索，直到 2023 年 2 月，没有时间限制。使用随机效应模型进行荟萃分析，仅考虑描述 AD 患者 VEGF 浓度的病例对照出版物来计算汇总效应大小。
在系统文献检索中，有 6 项和 13 项研究符合评估 AD 患者 CSF 和血清 VEGF 浓度的纳入标准。该荟萃分析共纳入 2380 名 AD 患者和 5368 名健康对照者。在荟萃分析的随机效应模型下，AD 患者 CSF 和血清 VEGF 浓度的合并 SMD 分别为-0.13（95%CI，-0.42-0.16）和 0.23（95%CI，-0.27-0.73）。Meta 回归分析结果表明，论文质量评分和参与者的女性比例并不影响 VEGF 浓度与 AD 风险的相关性。然而，患者的平均年龄显著影响 CSF VEGF 浓度与 AD 风险的相关性（P=0.051）。AD 患者疾病严重程度存在统计学显著的亚组效应，这会改变血清 VEGF 浓度与 AD 风险的相关性（P<0.01），亚组分析表明，研究地点会改变 CSF 和血清 VEGF 浓度与 AD 风险的相关性（P<0.01）。
结果表明，血清 VEGF 浓度随着 VEGF 表达的增加而升高，AD 患者的 VEGF 水平随着疾病严重程度的增加而降低。因此，除了在疾病的最早阶段检测 AD 外，血清 VEGF 还可能成为一种有前途的生物标志物，用于监测疾病并评估疾病的临床过程。
