More recent data suggest that the APOE-ε2 allele might prolong survival,[8–11] but other studies do not support such an association,[12,13] and have even implicated the ε2 allele as a detrimental factor in cerebral small-vessel disease,[14] dysbetalipoproteinemia,[15] and aggressiveness of certain cancer.[16] A better understanding of the benefits and risks associated with APOE-ε2 carrier status, above and beyond the absence of the ε4 allele, could lead to novel preventive and treatment options for a wide variety of conditions to promote healthy aging and longevity. Here, APOE is linked to cerebral small vessel disease.