早期APP/PS1雌性小鼠血浆脂质组学及其与大脑的关系:它受发情周期的影响吗?

IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Alzheimer's Research & Therapy Pub Date : 2024-08-14 DOI:10.1186/s13195-024-01549-x
Laura Ferré-González, Ángel Balaguer, Marta Roca, Artemis Ftara, Ana Lloret, Consuelo Cháfer-Pericás
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引用次数: 0

摘要

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,血脂在大脑中扮演着重要角色,在神经退行性病变中可能出现失调。具体来说,血浆脂质水平受损可预测早期老年痴呆症的诊断。本研究旨在确定早期AD雌性小鼠模型中发生改变的主要血浆脂质,并评估它们与脑脂质组的关系。此外,还对发情周期可能参与脂质代谢进行了评估:方法:收集、处理和分析5月龄野生型(n = 10)和APP/PS1(n = 10)雌性小鼠的血浆样本,采用基于脂质体质谱的方法进行分析。采用单变量和多变量方法进行统计分析,以确定各组间与AD相关的显著脂质差异。此外,还进行了细胞学检测以确认发情周期阶段:结果:血浆中检测出 3300 种脂质,其中 18 种脂质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、磷脂酰胆碱和醚键磷脂酰胆碱在 AD 早期升高;而其他磷脂酰胆碱、磷脂酰乙醇胺、神经酰胺和醚键磷脂酰乙醇胺在 AD 早期降低。根据一些脂质变量开发的多变量方法显示出较高的诊断指数(灵敏度 70%、特异度 90%、准确度 80%)。从大脑和血浆脂质组中观察到了一些显著的相关性,主要是在甘油磷脂家族中。此外,根据发情周期阶段的不同,血浆和大脑脂质也存在一些差异:因此,在小鼠雌性AD的早期阶段,可以发现血浆中的脂质发生了改变,大多数脂质亚族与脑脂质代谢有关,这表明一些脂质可能是AD的生物标志物。此外,发情周期监测可能与雌性研究相关。
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Plasma lipidomics in early APP/PS1 female mouse model and its relationship with brain: Is it affected by the estrous cycle?

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.

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来源期刊
Alzheimer's Research & Therapy
Alzheimer's Research & Therapy 医学-神经病学
CiteScore
13.10
自引率
3.30%
发文量
172
审稿时长
>12 weeks
期刊介绍: Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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