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Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum
Liu, Ying1; Tan, Lan1,2; Wang, Hui-Fu2; Liu, Yong4; Hao, Xiao-Ke3; Tan, Chen-Chen1; Jiang, Teng2; Liu, Bing4; Zhang, Dao-Qiang3; Yu, Jin-Tai1,2,5; Alzheimer's Dis Neuroimaging
Source PublicationMOLECULAR NEUROBIOLOGY
2016-09-01
Volume53Issue:7Pages:4539-4547
SubtypeArticle
AbstractThe apolipoprotein E epsilon 4 (APOE epsilon 4) allele is the most important genetic risk factor for Alzheimer's disease (AD); however, the underlying mechanisms responsible for it remain controversial. We used the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to examine the influence of APOE epsilon 4 dose on clinical and neuroimaging biomarkers across the AD spectrum (from cognitive normal to AD patients with severe cognitive impairment). A total of 1718 participants from the ADNI cohort were selected, and we evaluated the impact of epsilon 4 dose on cerebrospinal fluid (CSF) levels' Abeta1-42 (A beta(1-42)), tau, and phosphorylated-tau (p-tau); cortical amyloid deposition (Florbetapir-PET-AV45); brain atrophy (MRI); brain metabolism (FDG-PET); hippocampal metabolism; and cognitive declines, through different cognitive subgroups. We found that (1) epsilon 4 was associated with decreased CSF beta-amyloid (A beta(1-42)) and increased cerebral A beta deposition across the AD spectrum; (2) increased CSF tau, P-tau and cerebral hypometabolism, hippocampal atrophy, and cognition decline were all associated with APOE epsilon 4 in prodromal AD stage; (3) increased CSF tau, P-tau and cerebral hypometabolism appear to begin earlier than hippocampal atrophy and cognitive decline. We hypothesized that APOE epsilon 4 increases cerebral amyloid-beta (A beta) deposition in all the stages of AD development, and also influences A beta-initiated cascade of downstream neurodegenerative effects, thereby increasing the risk of AD.
KeywordAlzheimer's Disease Apoe Amyloid Beta Biomarker Adni
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1007/s12035-015-9388-7
WOS KeywordPOSITRON-EMISSION-TOMOGRAPHY ; AMYLOID-BETA PEPTIDE ; RATING-SCALE SUM ; APOLIPOPROTEIN-E ; CEREBROSPINAL-FLUID ; INITIATIVE ADNI ; GENETIC RISK ; DEMENTIA ; BRAIN ; LOAD
Indexed BySCI
Language英语
Funding OrganizationADNI (National Institutes of Health)(U01 AG024904) ; National Institute on Aging ; Alzheimer's Drug Discovery Foundation ; BioClinica, Inc ; Biogen Idec Inc ; Bristol-Myers Squibb Co ; F. Hoffmann-LaRoche Ltd ; Genetech, Inc ; GE Healthcare ; Innogenetics, NV ; IXICO Ltd ; Janssen Alzheimer Immunotherapy Research & Development LLC ; Medpace, Inc ; Merck Co, Inc ; Meso Scale Diagnostics, LLC ; NeuroRx Research ; Novartis Pharmaceuticals, Co ; Pfizer, Inc ; Piramal Imaging ; Servier ; Synarc Inc ; Takeda Pharmaceutical Co. ; Canadian Institutes of Health Research ; Northern California Institute for Research and Education ; National Natural Science Foundation of China(81471309 ; Shandong Provincial Outstanding Medical Academic Professional Program ; Qingdao Key Health Discipline Development Fund ; Qingdao Outstanding Health Professional Development Fund ; 81371406 ; 81171209)
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000380678600023
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/12175
Collection脑网络组研究中心
Affiliation1.Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
2.Nanjing Med Univ, Qingdao Municipal Hosp, Dept Neurol, Nanjing, Jiangsu, Peoples R China
3.Nanjing Univ Aeronaut & Astronaut, Dept Comp Sci & Engn, Nanjing, Jiangsu, Peoples R China
4.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing, Peoples R China
5.Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94158 USA
Recommended Citation
GB/T 7714
Liu, Ying,Tan, Lan,Wang, Hui-Fu,et al. Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum[J]. MOLECULAR NEUROBIOLOGY,2016,53(7):4539-4547.
APA Liu, Ying.,Tan, Lan.,Wang, Hui-Fu.,Liu, Yong.,Hao, Xiao-Ke.,...&Alzheimer's Dis Neuroimaging.(2016).Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum.MOLECULAR NEUROBIOLOGY,53(7),4539-4547.
MLA Liu, Ying,et al."Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum".MOLECULAR NEUROBIOLOGY 53.7(2016):4539-4547.
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