APOE and Alzheimer disease: Although overall lipid subclasses did not differ significantly between two groups (Extended Data Fig. 6b), APOE4/4 BDEVs exhibited significantly increased levels of free fatty acids (FFAs), particularly FFA 18:2, 16:1, 12:0, and 20:3, as well as sphingomyelin SM N25:0, while FFA 15:0, 17:0 and phosphatidylserine (PS) 16:0–18:2 and Lysophosphatidylcholine (LPC) A16:0 was significantly downregulated compared to APOE3/3 BDEVs (Fig. 2a, b, and Supplementary Table 2), suggesting that altered fatty acid metabolism in AD brain20 is reflected in the lipid composition of BDEVs.