title: Association between NME8 locus polymorphism and cognitive decline, cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease.
abstract: Recently, a large meta-analysis of five genome wide association studies (GWAS) identified a novel locus (rs2718058) adjacent to NME8 that played a preventive role in Alzheimer's disease (AD). However, this link between the single nucleotide polymorphism (SNP) rs2718058 and the pathology of AD have not been mentioned yet. Therefore, this study assessed the strength of association between the NME8 rs2718058 genotypes and AD-related measures including the cerebrospinal fluid (CSF) amyloid beta, tau, P-tau concentrations, neuroimaging biomarkers and cognitive performance, in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We used information of a total of 719 individuals, including 211 normal cognition (NC), 346 mild cognitive impairment (MCI) and 162 AD. Although we didn't observe a positive relationship between rs2718058 and AD, it was significantly associated with several AD related endophenotypes. Among the normal cognitively normal participants, the minor allele G carriers showed significantly associated with higher CDRSB score than A allele carriers (P = 0.021). Occipital gyrus atrophy were significantly associated with NME8 genotype status (P = 0.002), with A allele carriers has more atrophy than the minor allele G carriers in AD patients; lateral ventricle (both right and left) cerebral metabolic rate for glucose (CMRgl) were significantly associated with NME8 genotype (P < 0.05), with GA genotype had higher metabolism than GG and AA genotypes in MCI group; the atrophic right hippocampus in 18 months is significantly different between the three group, with GG and AA genotypes had more hippocampus atrophy than GA genotypes in the whole group. Together, our results are consistent with the direction of previous research, suggesting that NME8 rs2718058 appears to play a role in lowering the brain neurodegeneration.
authors.affiliation: Department of Neurology, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China; Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Hao
authors.affiliation: Air Beijing Dongjiao Lane Community Health, Beijing, China.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Yang
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, Nanjing, China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
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, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China; Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000473:pathology; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D013879:Thioredoxins / Q000235:genetics*
chemical_list: D015415:Biomarkers; C452260:NME8 protein, human; D013879:Thioredoxins