APOE and Alzheimer disease: The major genetic risk factor for sporadic AD is the allelic state of the APOE genotype, with inheritance of the APOE4 allele markedly increasing disease risk.153,154 Recently, Rawat et al. investigated how APOE4 affected ABCA1 expression and function in vitro in astrocytes.155 The authors found that APOE4 decreased ABCA1 plasma membrane levels and increased ABCA1 co-localization with late endosomes via activation of ADP-ribosylation factor 6, thereby reducing cholesterol efflux and lipidation of APOE particles.