title: HLA-A2 Alleles Mediate Alzheimer's Disease by Altering Hippocampal Volume.
abstract: HLA-A is a locus of the major histocompatibility complex situated on chromosome 6p21.3. HLA-A has been shown to be associated with susceptibility to Alzheimer's disease (AD). In this study, we firstly investigated the association of gene variants in HLA-A and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA-A on AD pathogenesis. We selected the hippocampus, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). In hybrid population analysis, our results showed a marginally significant association between rs9260168 and the atrophy of the left parahippocampus (P = 0.007, Pc = 0.054), rs3823342 and the atrophy of the left parahippocampus (P = 0.014, Pc = 0.054), rs76475517, which only exists in Caucasians with HLA-A23 or HLA-A24 alleles, and the atrophy of the right amygdala (P = 0.010, Pc = 0.085) at baseline. In particular, the haplotype (TGACAAGG), as a surrogate marker of HLA-A2, was founded to be positively associated with the atrophy of the right hippocampus (P = 0.047) at baseline. Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subpopulation analysis. Our study provided preliminary evidences supporting HLA-A2 in Caucasians contribute to the risk of AD by modulating the alteration of hippocampal volume and HLA-A gene variants appear to play a role in altering AD-related brain structures on MRI.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Zi-Xuan
authors.initials: ZX
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: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266000, China.
authors.forename: Lin
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, Shandong Province, 266071, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, 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, Shandong Province, 266071, China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Tan
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, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, 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, Shandong Province, 266071, 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; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D015789:HLA-A2 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size
chemical_list: D015789:HLA-A2 Antigen
keywords: Alzheimer’s disease; Brain structure; Genetics; HLA; Neuroimaging