APOE and Onset: The ε4 allele of Apolipoprotein E (APOE) gene is the strongest risk factor for clinical sporadic late-onset AD, conferring an increased risk (i.e. odds ratio [OR]) of AD compared to APOE-ε3 homozygotes of up to 3.46 OR for ε4 heterozygotes and 13.04 OR for APOE-ε4 homozygotes6, with APOE-ε4 homozygosity having a near complete penetrance for Aβ positivity7.