Alzheimer's Disease Research Group, Instituto de Investigación Sanitaria La Fe, Avda de Fernando Abril Martorell, 106; 46026, Valencia, Spain.
Faculty of Mathematics, University of Valencia, Valencia, Spain.
Alzheimers Res Ther. 2024 Aug 14;16(1):183. doi: 10.1186/s13195-024-01549-x.
Alzheimer's disease (AD) is the most prevalent dementia, showing higher incidence in women. Besides, lipids play an essential role in brain, and they could be dysregulated in neurodegeneration. Specifically, impaired plasma lipid levels could predict early AD diagnosis. This work aims to identify the main plasma lipids altered in early AD female mouse model and evaluate their relationship with brain lipidome. Also, the possible involvement of the estrous cycle in lipid metabolism has been evaluated.
Plasma samples of wild-type (n = 10) and APP/PS1 (n = 10) female mice of 5 months of age were collected, processed, and analysed using a lipidomic mass spectrometry-based method. A statistical analysis involving univariate and multivariate approaches was performed to identify significant lipid differences related to AD between groups. Also, cytology tests were conducted to confirm estrous cycle phases.
Three hundred thirty lipids were detected in plasma, 18 of them showed significant differences between groups; specifically, some triacylglycerols, cholesteryl esters, lysophosphatidylcholines, phosphatidylcholines, and ether-linked phosphatidylcholines, increased in early AD; while other phosphatidylcholines, phosphatidylethanolamines, ceramides, and ether-linked phosphatidylethanolamines decreased in early AD. A multivariate approach was developed from some lipid variables, showing high diagnostic indexes (70% sensitivity, 90% specificity, 80% accuracy). From brain and plasma lipidome, some significant correlations were observed, mainly in the glycerophospholipid family. Also, some differences were found in both plasma and brain lipids, according to the estrous cycle phase.
Therefore, lipid alterations can be identified in plasma at early AD stages in mice females, with a relationship with brain lipid metabolism for most of the lipid subfamilies, suggesting some lipids as potential AD biomarkers. In addition, the estrous cycle monitoring could be relevant in female studies.
阿尔茨海默病（AD）是最常见的痴呆症，女性发病率更高。此外，脂质在大脑中起着重要作用，它们可能在神经退行性变中失调。具体来说，血浆脂质水平降低可能预测 AD 的早期诊断。本研究旨在鉴定早期 AD 雌性小鼠模型中改变的主要血浆脂质，并评估其与大脑脂质组学的关系。此外，还评估了发情周期对脂质代谢的可能影响。
收集 5 月龄野生型（n=10）和 APP/PS1 （n=10）雌性小鼠的血浆样本，使用基于脂质组学质谱的方法进行处理和分析。采用单变量和多变量方法进行统计分析，以确定与 AD 相关的组间显著脂质差异。此外，还进行细胞学检测以确认发情周期阶段。
在血浆中检测到 330 种脂质，其中 18 种在组间存在显著差异；具体而言，一些三酰甘油、胆固醇酯、溶血磷脂酰胆碱、磷脂酰胆碱和醚键连接的磷脂酰胆碱在早期 AD 中增加；而其他磷脂酰胆碱、磷脂酰乙醇胺、神经酰胺和醚键连接的磷脂酰乙醇胺在早期 AD 中减少。从一些脂质变量中开发了一种多变量方法，显示出较高的诊断指数（70%的敏感性、90%的特异性、80%的准确性）。从大脑和血浆脂质组学来看，观察到一些显著的相关性，主要在甘油磷脂家族中。此外，根据发情周期阶段，在血浆和大脑脂质中都发现了一些差异。
因此，在雌性小鼠的早期 AD 阶段可以在血浆中识别脂质改变，与大多数脂质亚家族的大脑脂质代谢有关，提示一些脂质可能作为 AD 的潜在生物标志物。此外，发情周期监测在女性研究中可能很重要。
