ApoE4 makes microglia trem2bling

The ApoE-Trem2 pathway links two of the most important genetic risk variants for sporadic Alzheimer's disease. In this issue of Neuron, Gratuze and colleagues1 report that Trem2 deficiency further aggravates neurodegeneration in tau mutant mice expressing human ApoE4. Together with previous work, this study points to a complex interaction and highlights the need for studying molecular interactions on all human ApoE variants.