The alleles of rs3846662 differentially affect HMGCR exon 13 splicing, statin responsiveness, LDL cholesterol and potentially AD risk. Individuals carrying the rs3846662_G allele are prone to retain HMGCR exon 13, resulting in a greater proportion full-length HMGCR mRNA (% HMGCR_FL) and thus higher LDL cholesterol as a result of increased cellular HMGCR activity. Consequently, AD risk may be increased in these individuals due to a peripheral effect on plasma LDL and/or a central effect on HMGCR. Individuals carrying rs3846662_G, who are prone to both increased LDL and AD risk, are also predicted to be more responsive to stain therapy than individuals homozygous for the rs3846662_A allele (who tend to inefficiently splice HMGCR exon 13). Thus, rs3846662 genotype may not only increase AD risk but may also help separate potential responders from non-responders in statin trials to prevent AD.