背景:阿尔茨海默病(AD)是最常见的痴呆症,女性发病率较高。此外,脂质在大脑中起着至关重要的作用,它们可能在神经变性中失调。具体来说,血脂水平受损可预测AD的早期诊断。这项工作旨在确定早期AD雌性小鼠模型中主要的血浆脂质改变,并评估其与脑脂质组的关系。此外,已经评估了发情周期可能参与脂质代谢。
方法:收集5月龄的野生型(n=10)和APP/PS1(n=10)雌性小鼠的血浆样本,已处理,并使用基于脂质组学质谱的方法进行分析。进行涉及单变量和多变量方法的统计分析以鉴定组间与AD相关的显著脂质差异。此外,进行细胞学检查以确认发情周期阶段。
结果:在血浆中检测到三百三十脂质,其中18个显示出组间的显著差异;特别是,一些三酰甘油,胆固醇酯,溶血磷脂酰胆碱,磷脂酰胆碱,和醚连接的磷脂酰胆碱,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,在早期AD中,醚连接的磷脂酰乙醇胺减少。从一些脂质变量中开发了一种多变量方法,显示高诊断指标(70%灵敏度,90%特异性,80%的准确度)。从大脑和血浆脂质组,观察到一些显著的相关性,主要是甘油磷脂家族。此外,在血浆和脑脂质中发现了一些差异,根据发情周期阶段。
结论:因此,在雌性小鼠的早期AD阶段,可以在血浆中发现脂质改变,与大多数脂质亚家族的大脑脂质代谢有关,提示一些脂质作为潜在的AD生物标志物。此外,发情周期监测可能与女性研究有关。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.