APOE and Alzheimer disease: The ε4 allele of APOE 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 homozygotes 8, with APOE-ε4 homozygosity having a near complete penetrance for Aβ positivity 9.