With respect to the latter, a retrospective study conducted by Xia et al. (1996) showed that a particular allele in the SNCA promoter was enriched 4-fold in cognitively healthy ApoE4 carriers as compared to ApoE4 carriers with AD, suggesting that this SNCA polymorphism has a protective effect against the strongest known risk factor for AD. This evidence concerns the gene APOE and Alzheimer disease.