Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, 27 South Zhongguancun Avenue, Beijing, 100081, China.
J Mol Neurosci. 2018 Jul;65(3):289-300. doi: 10.1007/s12031-018-1100-8. Epub 2018 Jun 28.
Accumulating evidence suggest that aberrations of neurotrophic factors are involved in the etiology and pathogenesis of Alzheimer's disease (AD), but clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic factor levels in AD is necessary. We performed a systematic review of blood, CSF, and post-mortem brain neurotrophic factor levels in patients with AD compared with controls and quantitatively summarized the clinical data in blood and CSF with a meta-analytical technique. A systematic search of PubMed and Web of Science identified 98 articles in this study (with samples more than 9000). Random effects meta-analysis demonstrated that peripheral blood BDNF levels were significantly decreased in AD patients compared with controls. However, blood NGF, IGF, and VEGF did not show significant differences between cases and controls. In CSF, random effects meta-analysis showed significantly deceased BDNF and increased NGF levels in patients with AD, whereas IGF and VEGF did not show significant differences between the AD group and control group. In addition, 23 post-mortem studies were included in the systematic review. Although data from post-mortem brains were not always consistent across studies, most studies suggested decreased BDNF and increased (pro)NGF levels in hippocampus and neocortex of patients with AD. These results provide strong clinical evidence that AD is accompanied by an aberrant neurotrophin profile, and future investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and therapeutic targets for AD may be warranted.
越来越多的证据表明，神经营养因子的异常与阿尔茨海默病 (AD) 的病因和发病机制有关，但临床数据并不一致。因此，有必要对 AD 患者的神经营养因子水平进行荟萃分析。我们对 AD 患者与对照组相比的血液、CSF 和死后大脑神经营养因子水平进行了系统评价，并采用荟萃分析技术定量总结了血液和 CSF 中的临床数据。通过对 PubMed 和 Web of Science 的系统搜索，本研究共确定了 98 篇文章（样本量超过 9000 例）。随机效应荟萃分析表明，AD 患者外周血 BDNF 水平明显低于对照组。然而，血液 NGF、IGF 和 VEGF 在病例组和对照组之间没有显示出显著差异。在 CSF 中，随机效应荟萃分析显示 AD 患者的 BDNF 水平明显降低，NGF 水平升高，而 IGF 和 VEGF 在 AD 组和对照组之间没有显著差异。此外，本系统评价还纳入了 23 项尸检研究。尽管尸检脑组织的数据在不同研究中并不总是一致，但大多数研究表明 AD 患者海马和新皮层的 BDNF 减少和（pro）NGF 增加。这些结果为 AD 患者伴有异常神经肽谱提供了有力的临床证据，未来对神经营养因子作为 AD 生物标志物（尤其是 CSF BDNF 和 NGF）和治疗靶点的研究可能是必要的。
