Journal
PLOS ONE
Volume 9, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0114777
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Categories
Funding
- ADNI (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Bio-Clinica, Inc
- Biogen Idec Inc
- Bristol-Myers Squibb Co, F. HoffmannLaRoche Ltd and Genetech, Inc
- GE Healthcare
- Innogenetics, NV
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development LLC
- Medpace, Inc
- Merck Co, Inc
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Novartis Pharmaceuticals, Co, Pfizer, Inc
- Piramal Imaging
- Servier
- Synarc Inc
- Takeda Pharmaceutical Co
- ADNI clinical sites in Canada
- National Natural Science Foundation of China [81171209, 81371406, 81000544]
- Jiangsu Natural Science Foundation for Distinguished Young Scholar [BK20130034]
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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.
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