However, Wong and colleagues have observed in human AD brains and transgenic mice tissue that 25-hydrocholesterol, a relevant inflammatory mediator produced by microglia, promotes IL-1β mediated neuroinflammation in an apoE isoform-dependent trend (apoE4 >  > apoE3/apoE2), and apoE4-expressing microglia produce higher levels of 25-hydrocholesterol [285]. This evidence concerns the gene APOE and Alzheimer disease.