Transcriptome Analyses in BV2 microglial cells following treatment with amino-terminal fragments of apolipoprotein E
This study assessed the effects of amino terminal ApoE4 fragments (residues 1-151) on modulating the transcriptome of BV2 microglial cells. Treatment with amino terminal ApoE4 fragments caused the upregulation of nearly four-thousand genes, and further analysis revealed a significant upregulation of genes related to the inflammatory immune response. As a control, an amino terminal ApoE3 fragment was tested and produced a similar but reduced level of upregulation of an identical set of genes.  This set of genes affected pathways including Toll receptor signaling, chemokine/cytokine signaling and apoptosis signaling. Additionally, each treatment regulated a unique set of genes. Amino terminal ApoE3 fragments uniquely regulated 14 times as many genes (1,674), many of which are involved in physiological functions within microglia.  Amino terminal ApoE4 fragments uniquely upregulated 119 genes, with many of the top upregulated genes having unknown functions. Our results suggest that while amino terminal ApoE3 fragments may serve a more physiological role in microglia amino terminal ApoE4 fragments may activate genes with a more pathological purpose. These data support the hypothesis that the link between harboring the APOE4 allele and dementia risk could be enhanced inflammation through activation of microglia. Overall design: Total RNA-sequencing was performed to assess transcriptional changes that occurred in BV2 microglial cells following treatment with amino-terminal fragment (residues 1-151) of ApoE4 or ApoE3.