Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer’s Disease Spectrum

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• 作者：Ying Liu ; Lan Tan ; Hui-Fu Wang ; Yong Liu ; Xiao-Ke Hao…
• 关键词：Alzheimer’s disease ; APOE ; Amyloid beta ; Biomarker ; ADNI
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：53
• 期：7
• 页码：4539-4547
• 全文大小：779 KB
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• 作者单位：Ying Liu (1)
  Lan Tan (1) (2)
  Hui-Fu Wang (2)
  Yong Liu (4)
  Xiao-Ke Hao (3)
  Chen-Chen Tan (1)
  Teng Jiang (2)
  Bing Liu (4)
  Dao-Qiang Zhang (3)
  Jin-Tai Yu (1) (2) (5)
  Alzheimer’s Disease Neuroimaging Initiative
  
  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China
  2. Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China
  4. Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
  3. Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
  5. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182
• 卷排序：53

文摘

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 (Aβ_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) ε4 was associated with decreased CSF beta-amyloid (Aβ_1-42) 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. Keywords Alzheimer’s disease APOE Amyloid beta Biomarker ADNI