APOE and Alzheimer disease: Humans, unlike other mammals, have 3 common alleles of the apolipoprotein (apo) E gene (APOE), the ε2 (APOE2), ε3 (APOE3), and ε4 (APOE4) alleles [19], and inheritance of APOE4 is associated with increased risk, earlier onset, or poorer clinical outcome for a number of neurologic diseases that broadly overlap with those associated with innate immune activation cited above: AD, PD, ALS, traumatic brain injury, and HIV-encephalitis [20-28]; at least for AD, inheritance of APOE2 also is associated with apparent neuroprotection [29].