title: Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.
abstract: Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease.
  
  
  
  We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations.
  
  
  
  There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores.
  
  
  
  Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niaosung, Kaohsiung, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Hsu
authors.affiliation: Psychiatric Department of Taipei Veterans General Hospital, Taipei, Taiwan.|Psychiatric Division, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.
authors.forename: Nai-Ching
authors.initials: NC
authors.lastname: Chen
authors.affiliation: Psychiatric Department of Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Mu-En
authors.initials: ME
authors.lastname: Liu
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niaosung, Kaohsiung, Taiwan.
authors.forename: Chen-Chang
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niaosung, Kaohsiung, Taiwan.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.
authors.forename: Weng-Neng
authors.initials: WN
authors.lastname: Chang
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung County, 833, Taiwan. neur099@adm.cgmh.org.tw.
authors.forename: Chiung-Chih
authors.initials: CC
authors.lastname: Chang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics*; D001931:Brain Mapping; D005260:Female; D005838:Genotype; D006801:Humans; D021621:Imaging, Three-Dimensional; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: D053583:Interleukin-1beta
keywords: Alzheimer’s disease; Anatomical structural covariance; Executive control network; Interleukin-1 beta polymorphism; Salience network