title: Sex moderates the effects of the Sorl1 gene rs2070045 polymorphism on cognitive impairment and disruption of the cingulum integrity in healthy elderly.
abstract: The SORL1 rs2070045 polymorphism was reported to be associated with SorLA expression in the brain and the risk of late-onset Alzheimer's disease (AD). However, the influence of this polymorphism on cognitive functioning is likely to be moderated by sex. This study aimed to examine the sex moderation on the effects of rs2070045 on neuropsychological performance and the cingulum integrity in Chinese Han population. In this study, 780 non-demented older adults completed a battery of neuropsychological scales. Diffusion tensor images (DTI) of 126 subjects were acquired. We adopted the atlas-based segmentation strategy for calculating the DTI indices of the bilateral cingulum and cingulum hippocampal part for each subject. We used a multivariate analysis of variance (MANOVA) to compare the cognitive performance and DTI differences between the rs2070045 genotype. Controlling for age, education, and the APOE ɛ4 status, the influence of sex on the effects of the rs2070045 polymorphism on executive function was observed. We also found an interaction between sex and the rs2070045 polymorphism on the white matter (WM) microstructure of the left cingulum hippocampal part. Furthermore, the mean diffusivity and axial diffusivity of the tract were associated with Trail Making Test performance in T/T men. These results hint that sex moderates the association between the rs2070045 polymorphism and executive function, as well as the WM integrity of the left cingulum hippocampal part. Our findings underscore the importance of considering the influence of sex when examining the candidate genes for cognitive abilities and AD.
authors.affiliation: 1] State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China [2] BABRI Centre, Beijing Normal University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 1] BABRI Centre, Beijing Normal University, Beijing, China [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.affiliation: 1] BABRI Centre, Beijing Normal University, Beijing, China [2] Consulting Center of Biomedical Statistics, Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Chenlong
authors.initials: C
authors.lastname: Lv
authors.affiliation: 1] State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China [2] BABRI Centre, Beijing Normal University, Beijing, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Shu
authors.affiliation: Computational Image Analysis Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.affiliation: 1] State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China [2] BABRI Centre, Beijing Normal University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China [2] BABRI Centre, Beijing Normal University, Beijing, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Consulting Center of Biomedical Statistics, Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Liangping
authors.initials: L
authors.lastname: Hu
authors.affiliation: 1] State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China [2] BABRI Centre, Beijing Normal University, Beijing, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004522:Educational Status; D005260:Female; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics
chemical_list: D053327:Apolipoprotein E4; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human