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Impact of PICALM and CLU on Hippocampal Degeneration
Yang, Xianfeng1,2; Li, Jin3,4,5; Liu, Bing3,4,5; Li, Yonghui1; Jiang, Tianzi1,2,3,4,5
Source PublicationHUMAN BRAIN MAPPING
2016-07-01
Volume37Issue:7Pages:2419-2430
SubtypeArticle
AbstractPICALM and CLU are two major risk genes of late-onset Alzheimer's disease (LOAD), and there is strong molecular evidence suggesting their interaction on amyloid-beta deposition, hence finding functional dependency between their risk genotypes may lead to better understanding of their roles in LOAD development and greater clinical utility. In this study, we mainly investigated interaction effects of risk loci PICALM rs3581179 and CLU rs11136000 on hippocampal degeneration in both young and elderly adults in order to understand their neural mechanism on aging process, which may help identify robust biomarkers for early diagnosis and intervention. Besides volume we also assessed hippocampal shape phenotypes derived from diffeomorphic metric mapping and nonlinear dimensionality reduction. In elderly individuals (75.6 +/- 6.7 years) significant interaction effects existed on hippocampal volume (P < 0.001), whereas in young healthy adults (19.4 +/- 1.1 years) such effects existed on a shape phenotype (P = 0.01) indicating significant variation at hippocampal head and tail that mirror most AD vulnerable regions. Voxel-wise analysis also pointed to the same regions but lacked statistical power. In both cohorts, PICALM protective genotype AA only exhibited protective effects on hippocampal degeneration and cognitive performance when combined with CLU protective T allele, but adverse effects with CLU risk CC. This study revealed novel PICALM and CLU interaction effects on hippocampal degeneration along aging, and validated effectiveness of diffeomorphometry in imaging genetics study. (C) 2016 Wiley Periodicals, Inc.
KeywordPicalm Clu Interaction Hippocampus Alzheimer's Disease
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1002/hbm.23183
WOS KeywordALZHEIMERS-DISEASE ; IN-VIVO ; BRAIN ; ASSOCIATION ; ENDOCYTOSIS ; INDIVIDUALS ; LOCI ; APOE ; METAANALYSIS ; REPLICATION
Indexed BySCI
Language英语
Funding OrganizationNational Key Basic Research and Development Program (973)(2011CB707800) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB02030300) ; National Natural Science Foundation of China(91132301) ; Alzheimer's Disease Neuroimaging Initiative (ADNI ; DOD ADNI (Department of Defense)(W81XWH-12-2-0012) ; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering (ADNI) ; National Institutes of Health)(U01 AG024904)
WOS Research AreaNeurosciences & Neurology ; Radiology, Nuclear Medicine & Medical Imaging
WOS SubjectNeurosciences ; Neuroimaging ; Radiology, Nuclear Medicine & Medical Imaging
WOS IDWOS:000382488800005
Citation statistics
Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/10843
Collection脑网络组研究中心
Affiliation1.Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
2.Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia
3.Chinese Acad Sci, Inst Automat, CAS Ctr Excellence Brain Sci, Beijing 100190, Peoples R China
4.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing 100190, Peoples R China
5.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China
Recommended Citation
GB/T 7714
Yang, Xianfeng,Li, Jin,Liu, Bing,et al. Impact of PICALM and CLU on Hippocampal Degeneration[J]. HUMAN BRAIN MAPPING,2016,37(7):2419-2430.
APA Yang, Xianfeng,Li, Jin,Liu, Bing,Li, Yonghui,&Jiang, Tianzi.(2016).Impact of PICALM and CLU on Hippocampal Degeneration.HUMAN BRAIN MAPPING,37(7),2419-2430.
MLA Yang, Xianfeng,et al."Impact of PICALM and CLU on Hippocampal Degeneration".HUMAN BRAIN MAPPING 37.7(2016):2419-2430.
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