Wretlind Asger, Xu Jin, Chen Wenqiang, Velayudhan Latha, Ashton Nicholas J, Zetterberg Henrik, Proitsi Petroula, Legido-Quigley Cristina
King's College London, London, UK.
Steno Diabetes Center Copenhagen, Herlev, Denmark.
Alzheimers Dement. 2025 Aug;21(8):e70512. doi: 10.1002/alz.70512.
Alzheimer's disease (AD) is a devastating neurological disease that disproportionately affects women. This study aimed to investigate sex-specific single lipids associated with AD.
Plasma samples from 841 participants, comprising 306 individuals with AD, 165 with mild cognitive impairment (MCI), and 370 cognitively healthy controls were curated from the AddNeuroMed cohort. Lipidomics identified 268 single lipids for each sample. We investigated sex-specific associations from lipid modules and single lipids to AD and probed for causality with mediation analyses.
Three modules associated with AD in the female subset and one in the male subset (P < 0.05). In the female participants with AD, lipid families containing highly unsaturated fatty acids were reduced and those containing saturated lipids were increased (q value < 0.05). The effects of unsaturated phospholipids on AD were not mediated via cholesterol, low-density lipoprotein, or apolipoprotein B.
Women with AD have lower unsaturated plasma lipid levels compared to controls.
Lipid profiling showed lipid changes associated with Alzheimer's disease (AD) exclusively in women. Women with AD had fewer highly unsaturated lipids and more saturated lipids. Unsaturated phospholipids affected AD independently of cholesterol, low-density lipoprotein, or apolipoprotein B. Sex-stratified analysis is key to understanding the different manifestations of AD.
阿尔茨海默病（AD）是一种极具破坏性的神经疾病，对女性的影响尤为严重。本研究旨在调查与AD相关的性别特异性单一脂质。
从AddNeuroMed队列中选取了841名参与者的血浆样本，其中包括306名AD患者、165名轻度认知障碍（MCI）患者和370名认知健康对照者。脂质组学分析确定了每个样本中的268种单一脂质。我们研究了从脂质模块和单一脂质到AD的性别特异性关联，并通过中介分析探讨了因果关系。
在女性亚组中有三个模块与AD相关，在男性亚组中有一个模块与AD相关（P < 0.05）。在患有AD的女性参与者中，含有高度不饱和脂肪酸的脂质家族减少，而含有饱和脂质的脂质家族增加（q值 < 0.05）。不饱和磷脂对AD的影响不是通过胆固醇、低密度脂蛋白或载脂蛋白B介导的。
与对照组相比，患有AD的女性血浆不饱和脂质水平较低。
脂质谱分析显示，脂质变化仅在女性中与阿尔茨海默病（AD）相关。患有AD的女性高度不饱和脂质较少而饱和脂质较多。不饱和磷脂独立于胆固醇、低密度脂蛋白或载脂蛋白B影响AD。性别分层分析是理解AD不同表现的关键。
