title: Effect of CR1 Genetic Variants on Cerebrospinal Fluid and Neuroimaging Biomarkers in Healthy, Mild Cognitive Impairment and Alzheimer's Disease Cohorts.
abstract: The complement component (3b/4b) receptor 1 gene (CR1) is considered as one of the most important genetic susceptibility loci in Alzheimer's disease (AD). However, to date, few studies were performed to discover the possible effect of CR1 genetic variants on AD pathology in the brain. Here, we evaluated the potential role of CR1 common variants in AD-related pathology by assessing neuroimaging biomarkers and cerebrospinal fluid (CSF) proteins. Finally, a total of 812 subjects from the Alzheimer's disease Neuroimaging Initiative database and eight single nucleotide polymorphisms (SNPs) after quality control procedures are enrolled in our analysis. After applied to multiple linear regression models, significant associations were proved to exist between rs4844609 and amyloid deposition in cingulated, frontal, parietal, and temporal on florbetapir 18F amyloid positron emission tomography. In the analysis of the impacts of CR1 genetic variants on brain structures, three SNPs (rs12034383, rs3737002, and rs6691117) were significantly linked to the changes in volume of middle temporal. In addition, rs10779339 showed a negative connection with the cerebral metabolism rate of glucose in the right temporal on 18F-fluorodeoxyglucose PET imaging. However, no significant statistical findings were detected between CR1 genetic variants and CSF proteins (amyloid β, total-tau, and p-tau) at baseline diagnose or in the follow-up study of 2 years. The results of our study indicated that CR1 plays a vital role in AD pathology mainly by influencing Aβ deposition, brain structure, and glucose metabolism during AD progression.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.|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, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Lu
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, Qingdao Municipal Hospital, 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, Nanjing Medical University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China. dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. yu-jintai@163.com.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. yu-jintai@163.com.|Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China. yu-jintai@163.com.|Memory and Aging Center, Department of Neurology, University of California, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA, 94158, USA. yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D059906:Neuroimaging / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017463:Receptors, Complement 3b / Q000235:genetics*
chemical_list: D015415:Biomarkers; C509991:CR1 protein, human; D017463:Receptors, Complement 3b
keywords: Alzheimer’s disease; Amyloid deposition; Brain structure; CR1; CSF; Glucose metabolism; Neuroimaging