氧化应激和炎症代谢物与轻度认知障碍阿尔茨海默病脑脊液生物标志物的关联。
Association of oxidative stress and inflammatory metabolites with Alzheimer's disease cerebrospinal fluid biomarkers in mild cognitive impairment.
机构信息
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Metabolomics and Analytics Center, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
出版信息
Alzheimers Res Ther. 2024 Jul 30;16(1):171. doi: 10.1186/s13195-024-01542-4.
BACKGROUND
Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects.
METHODS
Targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LCMS) in 147 paired plasma-CSF samples from the Ace Alzheimer Center Barcelona and 58 CSF samples of MCI patients from the Mannheim/Heidelberg cohort. Linear regression was used to evaluate the association of metabolites with CSF levels of ATN biomarkers in the overall sample and stratified by Aβ-42 pathology and APOE genotype. We further evaluated the role of metabolites in MCI to AD dementia progression.
RESULTS
Increased CSF levels of PGF2α, 8,12-iso-iPF2α VI, and 5-iPF2α VI were significantly associated (False discovery rate (FDR) < 0.05) with higher p-tau levels. Additionally, 8,12-iso-iPF2α VI was associated with increased total tau levels in CSF. In MCI due to AD, PGF2α was associated with both p-tau and total tau, whereases 8,12-iso-iPF2α VI was specifically associated with p-tau levels. In APOE stratified analysis, association of PGF2α with p-tau and t-tau was observed in only APOE ε4 carriers while 5-iPF2α VI showed association with both p-tau and t-tau in APOE ε33 carriers. CSF levels of 8,12- iso-iPF2α VI showed association with p-tau and t-tau in APOE ε33/APOE ε4 carriers and with t-tau in APOE ε3 carriers. None of the metabolites showed evidence of association with MCI to AD progression.
CONCLUSIONS
Oxidative stress (8,12-iso-iPF2α VI) and inflammatory (PGF2α) biomarkers are correlated with biomarkers of AD pathology during the prodromal stage of AD and relation of PGF2α with tau pathology markers may be influenced by APOE genotype.
背景
异前列腺素和前列腺素是氧化应激和炎症的生物标志物。它们在阿尔茨海默病（AD）发病机制中的作用尚不清楚。在目前的研究中，我们旨在确定异前列腺素和前列腺素与轻度认知障碍（MCI）患者 AD 发病机制中的淀粉样蛋白、tau、神经退行性变（ATN）生物标志物（Aβ-42、p-tau 和 t-tau）之间的关联。
方法
使用液相色谱-质谱联用（LCMS）对来自巴塞罗那 Ace 阿尔茨海默病中心的 147 对血浆-CSF 样本和来自曼海姆/海德堡队列的 58 例 MCI 患者的 CSF 样本进行靶向代谢组学分析。线性回归用于评估代谢物与总体样本中 CSF 水平 ATN 生物标志物的关联，并按 Aβ-42 病理学和 APOE 基因型进行分层。我们进一步评估了代谢物在 MCI 向 AD 痴呆进展中的作用。
结果
CSF 中 PGF2α、8,12-iso-iPF2α VI 和 5-iPF2α VI 的水平升高与 p-tau 水平升高显著相关（错误发现率（FDR）<0.05）。此外，8,12-iso-iPF2α VI 与 CSF 中总 tau 水平升高相关。在 AD 所致的 MCI 中，PGF2α 与 p-tau 和总 tau 相关，而 8,12-iso-iPF2α VI 则与 p-tau 水平相关。在 APOE 分层分析中，仅在 APOE ε4 携带者中观察到 PGF2α 与 p-tau 和 t-tau 的关联，而 5-iPF2α VI 仅在 APOE ε33 携带者中与 p-tau 和 t-tau 均相关。CSF 中 8,12-iso-iPF2α VI 与 APOE ε33/APOE ε4 携带者的 p-tau 和 t-tau 以及 APOE ε3 携带者的 t-tau 相关。没有代谢物显示与 MCI 向 AD 进展相关的证据。
结论
氧化应激（8,12-iso-iPF2α VI）和炎症（PGF2α）生物标志物与 AD 发病前阶段 AD 病理的生物标志物相关，PGF2α 与 tau 病理标志物的关系可能受 APOE 基因型的影响。
Zotero 插件