In this study, to assess the lipidomic alterations associated with Tau pathology, we analyzed lipidomic profiling of the hippocampus tissues from PS19 wild-type mice aged 4.4 months, 7.5 months, and 11 months, as well as human tau-overexpressing PS19 mice aged 4.4 months (early-stage AD), 7.5 months (mid-stage AD), and 11 months (late-stage AD) using ultra-performance liquid chromatography trapped ion mobility spectrometry time-of-flight mass spectrometry (UPLC TIMS-TOF MS).

As a result of multivariate analysis, the score plot of principal component analysis showed a notable separation between the wild-type and tau group, especially in the late-stage (11 months).  However, there was no clear distinction in the early and mid-stages, suggesting that lipid changes in hippocampus tissue due to tau are particularly severe in late-stage AD compared to other stages. Specifically, in the late-stage tau group, the levels of cholesteryl ester, triacylglycerol, and ceramide were significantly increased compared to the other groups. In addition to the notable lipid accumulation observed in the late-stage, we identified changes in the lipid composition of hippocampus tissue as aging progressed from the early to late-stages.