APOE and Alzheimer disease: The main cause of reduced Aβ clearance in sporadic AD is likely APOE ɛ4, since the apoE4 protein isoform has reduced capacity to clear Aβ peptides compared with other apoE isoforms8, although it is possible that APOE ɛ4 may also contribute to increased AD risk by other mechanisms, for example, by affecting inflammation and neuronal repair15, 16.