title: Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Age-Related Interaction in Adult Lifespan.
abstract: Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21-92 years). Through voxel-based morphometry, we found that participants carrying SORL1 allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and SORL1 suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that SORL1 rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan.
authors.affiliation: Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chu-Chung
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Mu-En
authors.initials: ME
authors.lastname: Liu
authors.affiliation: Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.|Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Kao
authors.affiliation: Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kun-Hsien
authors.initials: KH
authors.lastname: Chou
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tong-Ru
authors.initials: TR
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human