We further showed that this neuroinflammation can be modulated therapeutically: HFD-fed Ldlr-/-.Leiden mice responded to a therapeutic antibody intervention targeting complement C5 (BB5.1 antibody) which was previously shown to decrease neuroinflammation in acute models of neurodegenerative disease (Fluiter et al., 2014; Michailidou et al., 2018) and atherosclerosis in this mouse model (Seidel et al., 2022). This evidence concerns the gene C5 and neurodegenerative disease.