title: Effect of EPHA1 genetic variation on cerebrospinal fluid and neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.
abstract: Ephrin type-A receptor 1 (EPHA1) (11771145) was documented to be one of the most strongly associated locus with Alzheimer's disease (AD) in a recent meta-analysis of five genome wide association studies. However, its contribution to the pathogenesis of AD remains unclear to date. Here, we addressed the role of EPHA1 in AD by investigating the influence of EPHA1 on cerebrospinal fluid and neuroimaging biomarkers in three clinical stages from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We did not detect significant association of EPHA1 with amyloid-β deposition or tau protein. However, the A-allele in the mild cognitive impairment group remarkably prevented hippocampal atrophy (partial correlation coefficient 2.812, 95% CI 0.651 to 4.973) at two-year follow-up. Additionally, AD subjects with the A-allele displayed less atrophy and greater cerebral metabolic rate for glucose (CMRgl) in the right lateral occipitotemporal gyrus (volume: partial correlation coefficient 540.10, 95% CI 247.26 to 832.95; CMRgl: partial correlation coefficient 0.056, 95% CI 0.024 to 0.087) and inferior temporal gyrus (volume: partial correlation coefficient 327.98, 95% CI 11.65 to 644.31; CMRgl: partial correlation coefficient 0.055, 95% CI 0.019 to 0.091) at baseline. This study suggests EPHA1 (rs11771145) interferes with the pathological alteration of the hippocampus and the lateral occipitotemporal and inferior temporal gyri throughout the AD process, leading to a lower risk of AD. However, the limited sample size and follow-up as well as the diversity across ethnicities precluded explanation of these findings.
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 Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
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: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
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, Nanjing Medical University, Nanjing, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
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 / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005947:Glucose / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D059906:Neuroimaging; D036082:Receptor, EphA1 / Q000235:genetics*
chemical_list: D015415:Biomarkers; D036082:Receptor, EphA1; D005947:Glucose
keywords: Alzheimer's Disease Neuroimaging Initiative (ADNI); Alzheimer's disease; Ephrin type-A receptor 1 (EPHA1); biomarker; cerebrospinal fluid; neuroimaging