背景:脂质运载蛋白-2(LCN2)与轻度认知障碍(MCI)和痴呆之间的关联越来越受到关注。然而,基于人群的研究结果不一致.因此,我们进行了必要的系统综述和荟萃分析,以分析和总结现有的基于人群的证据.
方法:PubMed,EMBASE,和WebofScience进行了系统搜索,直到2022年3月18日。进行Meta分析,以产生外周血和脑脊液(CSF)LCN2的标准平均差异(SMD)。进行了定性审查,以总结死后脑组织研究的证据。
结果:在外周血中,总体汇总结果显示,阿尔茨海默病(AD)之间的LCN2没有显着差异,MCI和对照组。进一步的亚组分析显示AD患者血清LCN2水平高于对照组(SMD=1.28[0.44;2.13],p=0.003),而血浆中的差异仍然微不足道(SMD=0.04[-0.82;0.90],p=0.931)。此外,当AD和对照组之间的年龄差异≥4岁时,AD的外周血LCN2较高(SMD=1.21[0.37;2.06],p=0.005)。在CSF中,LCN2在AD组之间没有发现差异,MCI和控制。然而,与对照组相比,血管性痴呆(VaD)的CSFLCN2更高(SMD=1.02[0.17;1.87],p=0.018),以及与AD相比(SMD=1.19[0.58;1.80],p<0.001)。定性分析支持AD相关区域脑组织中LCN2升高,尤其是在星形胶质细胞和小胶质细胞中;而在混合型痴呆(MD)中,LCN2在与梗塞相关的脑区增加,并在星形胶质细胞和巨噬细胞中过表达。
结论:AD和对照组之间外周血LCN2的差异可能受生物流体类型和年龄的影响。在整个AD的CSFLCN2中没有发现差异,MCI和对照组。相比之下,VaD患者的CSFLCN2升高。此外,LCN2在AD相关脑区和细胞中增加,而在MD的梗死相关脑区和细胞中。
The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence.
PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies.
In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer\'s disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥ 4 years (SMD =1.21 [0.37;2.06], p = 0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p < 0.001). Qualitative analysis supported that LCN2 was increased in the brain tissue of AD-related areas, especially in astrocytes and microglia; while LCN2 increased in infarct-related brain areas and over-expressed in astrocytes and macrophages in mixed dementia (MD).
The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.