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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.

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  • Authors+Show Affiliations

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    Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.

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    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.

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    Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.

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    Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

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    Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.

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    Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.

    ,

    Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.

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    Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

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    Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.

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    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.

    Source

    Molecular neurobiology 53:7 2016 09 pg 4539-47

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoprotein E4
    Biomarkers
    Cross-Sectional Studies
    Databases, Factual
    Disease Progression
    Female
    Genotype
    Humans
    Male
    Neuroimaging
    Neuropsychological Tests
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    26298664

    Citation

    Liu, Ying, et al. "Multiple Effect of APOE Genotype On Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum." Molecular Neurobiology, vol. 53, no. 7, 2016, pp. 4539-47.
    Liu Y, Tan L, Wang HF, et al. Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum. Mol Neurobiol. 2016;53(7):4539-47.
    Liu, Y., Tan, L., Wang, H. F., Liu, Y., Hao, X. K., Tan, C. C., ... Yu, J. T. (2016). Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum. Molecular Neurobiology, 53(7), pp. 4539-47. doi:10.1007/s12035-015-9388-7.
    Liu Y, et al. Multiple Effect of APOE Genotype On Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum. Mol Neurobiol. 2016;53(7):4539-47. PubMed PMID: 26298664.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum. AU - Liu,Ying, AU - Tan,Lan, AU - Wang,Hui-Fu, AU - Liu,Yong, AU - Hao,Xiao-Ke, AU - Tan,Chen-Chen, AU - Jiang,Teng, AU - Liu,Bing, AU - Zhang,Dao-Qiang, AU - Yu,Jin-Tai, AU - ,, Y1 - 2015/08/23/ PY - 2015/03/03/received PY - 2015/08/11/accepted PY - 2015/8/24/entrez PY - 2015/8/25/pubmed PY - 2018/1/18/medline KW - ADNI KW - APOE KW - Alzheimer’s disease KW - Amyloid beta KW - Biomarker SP - 4539 EP - 47 JF - Molecular neurobiology JO - Mol. Neurobiol. VL - 53 IS - 7 N2 - 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. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/26298664/Multiple_Effect_of_APOE_Genotype_on_Clinical_and_Neuroimaging_Biomarkers_Across_Alzheimer's_Disease_Spectrum_ L2 - https://dx.doi.org/10.1007/s12035-015-9388-7 DB - PRIME DP - Unbound Medicine ER -