강수민 (연세대학교 화학과)

문명희 (연세대학교 화학과)

강수민 (연세대학교 화학과)

문명희 (연세대학교 화학과)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that increasingly affects aging populations. Despite active research, its pathogenesis remains unclear and no curative treatment exists. This highlights the urgent need for early diagnostic strategies and reliable biomarkers. Although genomics and proteomics have been widely studied in AD, lipidomics remains underexplored, despite the crucial roles of lipids in neuronal membranes, inflammation, and signaling.

In this study, we carried out a quantitative lipidomic analysis using nanoflow UHPLC-ESI-MS/MS on plasma and five distinct brain regions—hippocampus, olfactory bulb, cortex, thalamus, and cerebellum—collected from 5xFAD transgenic mice and their wild-type counterparts. A total of 610 lipid species in plasma and 503 in brain tissue were identified and classified into 21 major lipid classes.

PCA, volcano plots, and other analyses revealed brain region- and lipid class–specific alterations. Notably, PLA2 and ACAT pathway dysregulation was observed. Aβ-induced oxidative stress may activate PLA2, causing PC and PE depletion and LPC, LPA, and DG accumulation, suggesting membrane disruption. ACAT abnormalities were reflected in early CE accumulation followed by later-stage depletion.

These results indicate strong links between lipid dysregulation and AD pathology, suggesting PLA2 and ACAT as potential therapeutic targets.