APOE4 is recognised to induce pericyte degeneration and BBB breakdown by interfering with TREM2 signalling, which plays a role in microglial dysfunction, and various other proinflammatory signalling pathways.105, , -108 In a recent study, BBB breakdown was investigated in APOE4 carriers who were either cognitively normal or at the earliest symptomatic stage of AD.105 This showed that BBB breakdown in hippocampal and parahippocampal regions was greater in APOE4 carriers compared to non-carriers, and also in patients diagnosed with early AD compared to the cognitively normal. The gene discussed is TREM2; the disease is Alzheimer disease.