Effect Of HMGCR Genetic Variation On Neuroimaging Biomarkers In Healthy, Mild Cognitive Impairment And Alzheimer’s Disease Cohorts

As we all know, Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disease that it has become a considerable public health issue in the worldwide. It is characterized by formation of amyloid plaque, neurofibrillary tangles and necrosis of neuron. However,it is remain largely unclear about the mechanisms underlying AD onset and progression.3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) can encodes part of the statin-binding domain of the enzyme.This enzyme serves as the rate-limiting step in cholesterol synthesis in all mammalian cells. High cholesterol levels may perform a function in AD pathology. So HMGCR can be seen as a strong functional AD candidate gene.In our study, we enrolled in 812 subjects from the Alzheimer’s disease Neuroimaging Initiative dataset. Therefore, we evaluated the potential role of HMGCR (rs3846662) in AD-related pathology by assessing neuroimaging biomarkers getting from this dataset. Our rasearch shows it is possible that HMGCR (rs3846662) could be involved in preventing the atrophy of right entorhinal (P=0.03385) and left hippocampus (P=0.01839) in the follow-up research of two years. What’s more, in right temporal it lowered the drop rate of glucose metabolism both at baseline and the two-year follow up. We then further validated them in three different sub-groups (the AD, mild cognitive impairment (MCI), normal control (NC)). In the MCI cohort,all the results about the relation was confirmed. But we didn’t discover rs3846662 have any connection with Aβ deposition. The results of our study showed that HMGCR (rs3846662) plays a key role in AD pathology mainly by affecting brain structure and glucose metabolism during AD progression.