Lipid profiling reveals a deficit of lipids with unsaturated fatty acids in women with Alzheimer’s disease

Introduction 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. Methods 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. Results 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, LDL or ApoB. Discussion Women with AD have lower unsaturated blood lipid levels compared to controls.