Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou 510080, Guangdong, People's Republic of China; Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou 510080, Guangdong, People's Republic of China.
Department of Neurology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen 518067, Guangdong, People's Republic of China.
Ageing Res Rev. 2023 Aug;89:101984. doi: 10.1016/j.arr.2023.101984. Epub 2023 Jun 15.
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.
脂联素-2（LCN2）与轻度认知障碍（MCI）和痴呆的关联引起了越来越多的关注。然而，基于人群的研究结果并不一致。因此，我们进行了这项必要的系统综述和荟萃分析，以分析和总结现有基于人群的证据。
系统检索了 PubMed、EMBASE 和 Web of Science，截至 2022 年 3 月 18 日。进行荟萃分析以生成外周血和脑脊液（CSF）LCN2 的标准均数差（SMD）。进行定性综述以总结来自死后脑组织研究的证据。
在外周血中，LCN2 在阿尔茨海默病（AD）、MCI 和对照组之间没有显著差异。进一步的亚组分析显示，AD 患者的血清 LCN2 水平高于对照组（SMD=1.28[0.44；2.13]，p=0.003），而在血浆中差异无统计学意义（SMD=0.04[-0.82；0.90]，p=0.931）。此外，当 AD 与对照组的年龄差异≥4 岁时，AD 患者外周血 LCN2 升高（SMD=1.21[0.37；2.06]，p=0.005）。在 CSF 中，AD、MCI 和对照组之间的 LCN2 无差异。然而，与对照组相比，血管性痴呆（VaD）患者的 CSF LCN2 更高（SMD=1.02[0.17；1.87]，p=0.018），与 AD 相比也更高（SMD=1.19[0.58；1.80]，p<0.001）。定性分析支持 LCN2 在与 AD 相关的脑区，特别是星形胶质细胞和小胶质细胞中增加；而在混合性痴呆（MD）中，LCN2 在梗死相关脑区增加，在星形胶质细胞和巨噬细胞中过度表达。
AD 与对照组之间外周血 LCN2 的差异可能受生物流体类型和年龄的影响。AD、MCI 和对照组之间 CSF LCN2 无差异。相比之下，VaD 患者的 CSF LCN2 升高。此外，AD 患者的 LCN2 在与 AD 相关的脑区和细胞中增加，而在 MD 中则在梗死相关脑区和细胞中增加。
