By crossing the P301S Tau transgenic mice to those bearing a human ApoE knock-in allele or lacking ApoE completely, Shi et al. showed that P301S/ApoE E4 mice had significantly higher levels of intracellular Tau, more microglia activation and reactive astrogliosis compared to P301S mice bearing other ApoE variants, while the P301S mice lacking ApoE completely had the least tauopathy [38]. The gene discussed is APOE; the disease is tauopathy.