Compared to APOE4 noncarriers, the risk of AD is four-fold higher for APOE4 heterozygotes and 10-fold to 12-fold higher for APOE4/4 homozygotes [64] in populations based only on clinical diagnosis, rising to odds ratios of 4.6 and 25.4, respectively, for AD subjects diagnosed using CSF biomarkers [65]. Here, APOE is linked to Alzheimer disease.