Journal of Undergraduate Research


HMGCR, genetic modifier, Alzheimer's Disease, chronic neurodegenerative disorder


Life Sciences




Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that occurs predominantly later in life and represents the fourth most common cause of death in the developed world. Given the absence of curative treatment, discovering the factors related to the development of AD and the conversion from mild cognitive impairment (MCI) to AD is one of the most urgent medical mysteries affecting the aging population. The search for the identification of genes contributing to AD led to the identification of 695 candidate genes of which a surprising number are directly involved in lipid metabolism at the level of transport, synthesis, storage, and internalization of lipoproteins. Because 3-hydroxy-3methylglutaryl-CoA reductase (HMGCR) encodes for the enzyme that serves as the rate-limiting step in cholesterol synthesis, it is not surprising that recent studies have found an association between the HMGCR gene locus and AD. This association did not prove that HMGCR plays a role in AD, yet it does signal that studies analyzing the correlation between HMGCR and AD are needed. Our research focused on evaluating a single-nucleotide polymorphism (SNP) rs3846662 that has been reported to be involved in the regulation of HMGCR exon 13 skipping. Previous studies regarding rs3846662 state that subjects with the homozygous A (AA) allele exhibit a reduced risk of AD, a reduced conversion rate from MCI to AD, and a delayed age for onset of AD. Through genotyping the samples obtained through the Cache County Study on Memory, Health, and Aging and analyzing the data, we hope to confirm this report. Our project will further this study by analyzing more subgroups such as males with the G negative alleles, APOE4 positive alleles, and comparing the rate of decline after diagnosis of AD, survival rate, and the survival rate of males and female subgroups with different rs3846662 alleles.

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