Carrying the apolipoprotein E4 allele (APOE4), and not the APOE3 variant, is the strongest risk factor for developing Alzheimer’s disease (AD). But the underlying mechanism has remained elusive. Now, researchers at MIT and Mount Sinai have found that in brains carrying the APOE4 allele, lipid and cholesterol processes were dysregulated in oligodendrocytes and that this effect reduced myelination.