Fig. 8: Illustration of the APOE isoform-specific phospholipid composition effects on microglia transcriptome and phenotype in response to Aβ. | Nature Communications

Fig. 8: Illustration of the APOE isoform-specific phospholipid composition effects on microglia transcriptome and phenotype in response to Aβ.

From: Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease

Fig. 8: Illustration of the APOE isoform-specific phospholipid composition effects on microglia transcriptome and phenotype in response to Aβ.

Shotgun and LC-MS lipidomic analysis of APOE3 and APOE4 astrocyte conditioned media identified isoform-specific differences in phospholipid composition of APOE-containing lipoproteins. E3 or E4 lipoproteins co-infused with Aβ differentially impacted Aβ binding to microglia receptors (AXL, different CLECs clusters, TREM2, CD83, and others) this in turn affects genes expression of transcription factors (Spi1, Stat1, Nfkb, and Irf1) resulting in microglia activation. Active microglia demonstrate characteristic transcriptional profile, increased secretion of cytokines and chemokines thus facilitating chemotaxis and phagocytosis. Green arrows indicate an upregulation of that gene or category compared to the other APOE isoform.

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