title: Impact of Common Variations in PLD3 on Neuroimaging Phenotypes in Non-demented Elders.
abstract: Rare variants of phospholipase D3 (PLD3) have been identified as Alzheimer's disease (AD) susceptibility loci, whereas little is known about the potential role of common variants in the progression of AD. To examine the impact of genetic variations in PLD3 on neuroimaging phenotypes in a large non-demented population. A total of 261 normal cognition (NC) and 456 mild cognitive impairment (MCI) individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database are included in our analysis. Multiple linear regression models were applied to examine the association between four single-nucleotide polymorphisms (SNPs; rs7249146, rs4490097, rs12151243, and rs10407447) with the florbetapir retention on florbetapir 18F amyloid positron emission tomography (AV45-PET), the cerebral metabolic rate for glucose (CMRgl) on 18F-fluorodeoxyglucose PET (FDG-PET), and regional volume on magnetic resonance imaging (MRI) at baseline and in the cohort study. We did not detect any significant associations of PLD3 SNPs with florbetapir retention on AV45-PET. In the analysis of FDG-PET, rs10407447 was associated with the CMRgl in the left angular gyrus and bilateral posterior cingulate cortex in the MCI group. Regarding the MRI analysis, rs10407447 was also associated with bilateral inferior lateral ventricle and lateral ventricle volume in MCI group. The main findings of our study provide evidence that support the possible role of PLD3 common variants in influencing AD-related neuroimaging phenotypes. Nevertheless, further work is necessary to explain the functional mechanisms of differences and confirm the causal variants.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, Shandong, China.|Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
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: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, Shandong, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, Shandong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: Dao-Qiang
authors.initials: DQ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, Shandong, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China. dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, Shandong, 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; D003704:Dementia / Q000235:genetics*; D003710:Demography; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D059906:Neuroimaging; D010641:Phenotype; D010739:Phospholipase D / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D049268:Positron-Emission Tomography; D005090:Exodeoxyribonucleases
chemical_list: D019788:Fluorodeoxyglucose F18; D010739:Phospholipase D; C586092:PLD3 protein, human; D005090:Exodeoxyribonucleases
keywords: Alzheimer’s disease; Association; Neuroimaging; PLD3