Lipidome and Proteome of Astrocyte and Microglia ApoE Lipoprotein Reveal Differences Based on Cell Type and ApoE Isoform - PubMed
6 days ago
- #ApoE
- #lipidomics
- #Alzheimer’s disease
- Apolipoprotein E (ApoE) is the primary apolipoprotein in the central nervous system (CNS), crucial for brain metabolism and lipid homeostasis.
- ApoE is mainly secreted by astrocytes under normal conditions and by microglia in disease-related conditions.
- APOE has three major alleles: APOE2, APOE3, and APOE4, with APOE4 being the strongest genetic risk factor for late-onset Alzheimer's disease (AD).
- Lipidomics showed microglia-derived ApoE lipoproteins are enriched in cholesterol esters, while astrocyte-derived ApoE lipoproteins are enriched in sphingomyelin.
- Proteomics revealed astrocyte ApoE lipoproteins are involved in glucose metabolism and acute phase response, whereas microglia ApoE lipoproteins are involved in complement activation, synapse pruning, proteolysis, and innate immune response.
- ApoE4 lipoproteins from microglia were enriched in C1q and Lpl, while ApoE2 and ApoE3 lipoproteins were enriched in Ankk1 and ApoC1.
- The study highlights how ApoE lipoprotein cargo varies by cell type and isoform, influencing CNS homeostasis and disease pathogenesis.