Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study

3-Hydroxy-3-methylglutaryl coenzyme A reductase is associated with monitoring cholesterol levels. The presence of the single-nucleotide polymorphism rs3846662 introduces alternative splicing at exon 13; the exclusion of this exon leads to a reduction in total cholesterol levels. Lower cholesterol levels are linked to a reduction in Alzheimer's disease (AD) risk. The major allele of rs3846662, which encourages the splicing of exon 13, has recently been shown to act as a preventative allele for AD, especially in women. The purpose of our research was to replicate and confirm this finding. Using logistic regressions and survival curves, we found a significant association between AD and rs3846662, with a stronger association in individuals who carry the APOE e4 allele, supporting previously published work. The effect of rs3846662 on women is insignificant in our cohort. We confirmed that rs3846662 is associated with reduced risk for AD without gender differences; however, we failed to detect association between rs3846662 and delayed mild cognitive impairment conversion to AD for either of the APOE e4 allelic groups. •rs3846662 is associated with reduced risk for Alzheimer's disease.•Individuals with apolipoprotein E (APOE) e4 experience a greater protective effect from rs3846662.•Failed to detect gender-specific association of rs3846662, contrasting prior reports.•Failed to detect association between rs3846662 and delayed mild cognitive impairment conversion to AD.