Fragments containing the receptor-binding region (residues 136–150) and the lipid-binding region (residues 240–270) represent the minimal structure required for translocation, mitochondrial localization, and neurotoxicity (Mahley et al., 2006). Modified from Figure 4, Mahley, R.W., Weisgraber, K.H., and Huang, Y. Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc. Natl. Acad. Sci. USA 103: 5644–5651, 2006. © by the National Academy of Sciences.