Alzheimer’s disease (AD) is a progressive and incurable brain disorder that has been associated with structural changes in brain phospholipids (PLs), including diacyl species and ether-linked PLs known as plasmalogens. Most studies have characterized total changes in brain PL pools (e.g., choline plasmalogens), particularly in prefrontal cortex, but detailed and quantitative information on the molecular PL species impacted by the disease is limited. In this study, we used a comprehensive mass-spectrometry method to quantify diacyl and plasmalogen species, alkyl synthetic precursors of plasmalogens, and lysophospholipid degradation products of diacyl and plasmalogen PLs, in postmortem samples of prefrontal cortex from 21 AD patients and 20 age-matched controls. Total PLs were also quantified with gas-chromatography analysis of bound fatty acids following thin layer chromatography isolation. There was a significant 27% reduction in the concentration (nmol/g wet weight) of choline plasmalogen containing stearic acid (alkenyl group) and docosahexaenoic acid in AD compared to controls. Stearic acid concentration in total PLs was reduced by 26%. Our findings suggest specific changes in PLs containing stearic acid and docosahexaenoic acid in AD prefrontal cortex, highlighting structural and turnover PL pathways that could be targeted.

阿尔茨海默氏病 (AD) 是一种进行性和无法治愈的脑部疾病，与脑磷脂 (PL) 的结构变化有关，包括二酰基物质和醚连接的 PL，称为缩醛磷脂。大多数研究都描述了大脑 PL 库（例如，胆碱缩醛磷脂）的总体变化，特别是在前额叶皮质中，但有关受该疾病影响的分子 PL 种类的详细和定量信息是有限的。在这项研究中，我们使用综合质谱法对来自 21 名 AD 患者和 20 名年龄匹配的前额叶皮层的死后样本中的二酰基和缩醛磷脂种类、缩醛磷脂的烷基合成前体以及二酰基和缩醛磷脂 PL 的溶血磷脂降解产物进行量化控制。还通过薄层色谱分离后结合脂肪酸的气相色谱分析对总 PL 进行了量化。与对照组相比，AD 中含有硬脂酸（烯基组）和二十二碳六烯酸的胆碱缩醛磷脂的浓度（nmol/g 湿重）显着降低了 27%。总 PL 中的硬脂酸浓度降低了 26%。我们的研究结果表明 AD 前额皮质中含有硬脂酸和二十二碳六烯酸的 PL 发生了特定变化，突出了可以靶向的结构和周转 PL 途径。总 PL 中的硬脂酸浓度降低了 26%。我们的研究结果表明 AD 前额皮质中含有硬脂酸和二十二碳六烯酸的 PL 发生了特定变化，突出了可以靶向的结构和周转 PL 途径。总 PL 中的硬脂酸浓度降低了 26%。我们的研究结果表明 AD 前额皮质中含有硬脂酸和二十二碳六烯酸的 PL 发生了特定变化，突出了可以靶向的结构和周转 PL 途径。