CD4 and obesity due to melanocortin 4 receptor deficiency: To test our working hypothesis that HFD-induced obesity might accelerate disease manifestations via imposing systemic immune deregulation, we first analyzed the circulating immune cell landscape by mass cytometry (CyTOF), and found that the major effect was a trend of an increase of CD4+ T cells in the HFD-fed group in both WT and 5xFAD mice (Supplementary Fig. 6a–c).