title: Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum.
abstract: The apolipoprotein E ε4 (APOE ε4) 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 ε4 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 ε4 dose on cerebrospinal fluid (CSF) levels' Abeta1-42 (Aβ1-42), 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) ε4 was associated with decreased CSF beta-amyloid (Aβ1-42) and increased cerebral Aβ deposition across the AD spectrum; (2) increased CSF tau, P-tau and cerebral hypometabolism, hippocampal atrophy, and cognition decline were all associated with APOE ε4 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 ε4 increases cerebral amyloid-β (Aβ) deposition in all the stages of AD development, and also influences Aβ-initiated cascade of downstream neurodegenerative effects, thereby increasing the risk of AD.
authors: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors: Ying
authors: Y
authors: Liu
authors: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China. dr.tanlan@163.com.
authors: Lan
authors: L
authors: Tan
authors: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors: Hui-Fu
authors: HF
authors: Wang
authors: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors: Yong
authors: Y
authors: Liu
authors: Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors: Xiao-Ke
authors: XK
authors: Hao
authors: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors: Chen-Chen
authors: CC
authors: Tan
authors: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors: Teng
authors: T
authors: Jiang
authors: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors: Bing
authors: B
authors: Liu
authors: Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors: Dao-Qiang
authors: DQ
authors: Zhang
authors: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. yu-jintai@163.com.|Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China. yu-jintai@163.com.|Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. yu-jintai@163.com.
authors: Jin-Tai
authors: JT
authors: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D016208:Databases, Factual / Q000639:trends*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D059906:Neuroimaging / Q000639:trends*; D009483:Neuropsychological Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D016875:tau Proteins
keywords: ADNI; APOE; Alzheimer’s disease; Amyloid beta; Biomarker