To directly test whether theAPOEgenotype contributes to LD accumulation in microglia,APOE4/4and isogenicAPOE3/3iPS cells16were differentiated into microglia (iMG) as previously described17,18,19(Fig.3aand Extended Data Fig.5a). Live cell microscopy of iMG with a fluorescent dye for neutral lipid...
In addition, tau pathology was associated with strong gene expression changes in neurons, astrocytes, microglia, and oligodendrocytes, and some of these changes were partially attenuated with apoE4 reduction. In addition to relative synapse preservation with astrocyte apoE4 reduction, there was a ...
In response, astrocytes (FIG. 1, Step 2) and macrophages synthesize and release ApoE within the lesion to scavenge cholesterol from both cellular and myelin debris. Using the activity of the 3,3-hydroxy-methylglutaryl-CoA reductase (HMG-COA reductase) to monitor cholesterol synthesis, it was ...
After incubation, we depleted myelin debris by 30% isotonic Percoll (P1644; Sigma-Aldrich) gradient centrifugation and obtained mononuclear cell suspensions in DMEM/F12 medium with ice-cold 10% heat-inactivated fetal bovine serum. We prepared unstained controls from mixtures of different sample cell ...
APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) with APOE ε3/ε3 or ε4/ε4 genotype f
After incubation, we depleted myelin debris by 30% isotonic Percoll (P1644; Sigma-Aldrich) gradient centrifugation and obtained mononuclear cell suspensions in DMEM/F12 medium with ice-cold 10% heat-inactivated fetal bovine serum. We prepared unstained controls from mixtures of different sample cell ...