title: Effect of HMGCR genetic variation on neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.
abstract: Alzheimer's disease (AD) has become a considerable public health issue. The mechanisms underlying AD onset and progression remain largely unclear. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is a strong functional AD candidate gene because it encodes part of the statin-binding domain of the enzyme, which serves as the rate-limiting step in cholesterol synthesis in all mammalian cells. Here, we evaluated the potential role of HMGCR (rs3846662) in AD-related pathology by assessing neuroimaging biomarkers. We enrolled in 812 subjects from the Alzheimer's disease Neuroimaging Initiative dataset. In general, 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, it lowered the drop rate of glucose metabolism in right temporal. We then further validated them in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. All the results in the MCI groups confirmed the association. The results of our study indicated that HMGCR (rs3846662) plays a vital role in AD pathology mainly by influencing brain structure and glucose metabolism during AD progression.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Tan
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.|College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D064847:Multimodal Imaging; D059906:Neuroimaging / Q000379:methods*; D011379:Prognosis
chemical_list: D015415:Biomarkers; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: Alzheimer’s disease; Gerotarget; HMGCR; brain structure; glucose metabolism; neuroimaging