ABCA7 haplodeficiency disrupts microglial inflammatory responses and membrane trafficking

Carrying premature termination codons in one allele of the ABCA7 gene is associated with an increased risk for Alzheimer’s disease (AD). While the primary function of ABCA7 is to regulate the transport of phospholipids and cholesterol, ABCA7 is also involved in maintaining homeostasis of the immune system. Since inflammatory pathways causatively or consequently participate in AD pathogenesis, we studied the effects of Abca7 haplodeficiency in mice on brain immune responses under acute or chronic conditions. When the acute inflammation was induced through peripheral lipopolysaccharide (LPS) injection in control or heterozygous Abca7 knockout mice, partial ABCA7 deficiency diminished pro-inflammatory responses by impairing CD14 expression in the brain. We used Abca7 heterozygous and control mice. To investigate the relationship between Abca7 and inflammation in the brain, we injected lipopolysaccharide (LPS) into mice and then sacrificed the brains from these mice. Total RNAs of cortical brain were sequenced with Illumina HiSeq 4000 and Reads were mapped to the mouse genome mm10. Raw gene read counts, along with sequencing quality control, were generated using the Mayo Clinic RNA-sequencing analytic pipeline, MAP-RSeq Version 2.1.1.