title: Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE ε4.
abstract: In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Yun Yan
authors.initials: YY
authors.lastname: Su
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Imaging, Medical University of South Carolina Ashley River Tower, MSC 226, 25 Courtenay Dr, Charleston, SC, 29425, USA.
authors.forename: U Joseph
authors.initials: UJ
authors.lastname: Schoepf
authors.affiliation: Division of Cardiovascular Imaging, Medical University of South Carolina Ashley River Tower, MSC 226, 25 Courtenay Dr, Charleston, SC, 29425, USA.
authors.forename: Akos
authors.initials: A
authors.lastname: Varga-Szemes
authors.affiliation: Division of Cardiovascular Imaging, Medical University of South Carolina Ashley River Tower, MSC 226, 25 Courtenay Dr, Charleston, SC, 29425, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stubenrauch
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Zheng
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.|College of Civil Aviation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, 210016, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Shou Ju
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China.
authors.forename: Rong Feng
authors.initials: RF
authors.lastname: Qi
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China. cjr.luguangming@vip.163.com.
authors.forename: Guang Ming
authors.initials: GM
authors.lastname: Lu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China. kevinzhlj@163.com.
authors.forename: Long Jiang
authors.initials: LJ
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D053329:Apolipoprotein E2 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D000073216:Mental Status and Dementia Tests; D009154:Mutation; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology; D009483:Neuropsychological Tests; D053764:Presenilin-1 / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics*; D012146:Rest; D055815:Young Adult
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2
keywords: Alzheimer’s disease; Amyloid precursor protein; Apolipoprotein E; Default-mode network; Presenilin-1; Presenilin-2