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Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum.
Mol Neurobiol 2016; 53(7):4539-47MN

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+Show Affiliations

Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.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.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.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.No affiliation info available

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 -