title: Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.
abstract: The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD.
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
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, 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, Nanjing Medical University, Qingdao, China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Radiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Wan-Jiang
authors.initials: WJ
authors.lastname: Yu
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, China.|Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D051152:Clusterin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology*; D006801:Humans; D008297:Male; D059906:Neuroimaging; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D056811:Unfolded Protein Response
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D051152:Clusterin; D005947:Glucose