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Apolipoprotein E ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease.
J Alzheimers Dis. 2015; 45(3):781-95.JA

Abstract

The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD). Numerous studies have suggested that the modulation of APOE ε4 affects cognition and brain structure and function in healthy populations, particularly in the hippocampus, a key area associated with AD pathology. However, the effect of APOE ε4 allele on cognitive performance, hippocampal structural morphology, and specifically on functional characteristics in patients with AD remains poorly understood. Here, we employed a neuropsychological battery test and multi-modal structural MRI and resting-state functional MRI dataset to systematically investigate cognitive performance, hippocampal structural volume, and functional properties (including local low-frequency oscillating amplitude, intra-regional functional synchrony, and inter-regional functional connectivity) in 16 APOE ε4-carriers and 26 non-carriers at early stages of AD. Compared to non-carriers, APOE ε4-carriers exhibited poorer performance on recognition performance, but performed better on the late item generation of the verbal fluency task (associated with executive function). Structural imaging analysis revealed that APOE ε4-carriers exhibited smaller left hippocampal volumes compared to non-carriers, and the result remains significant after correcting for effects of brain size. Functional imaging analysis revealed that APOE ε4-carriers exhibited decreased amplitude of low-frequency fluctuations in the left hippocampus, non-significant changes in intra-regional synchronization within the hippocampus and decreased hippocampal functional connectivity predominantly in components of the default-mode network including the medial frontal and parietal cortices and the lateral temporal cortical regions. Taken together, our results showed APOE genotypic effects on the cognitive profile and hippocampal structural and functional characteristics in patients at early stages of AD, thus providing empirical evidence for the modulation of the APOE genotype on disease phenotype.

Authors+Show Affiliations

Dementia Care & Research Center, Peking University Institute of Mental Health; Key Laboratory for Mental Health, Ministry of Health (Peking University); Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China.State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, China Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, China.Dementia Care & Research Center, Peking University Institute of Mental Health; Key Laboratory for Mental Health, Ministry of Health (Peking University); Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China.Dementia Care & Research Center, Peking University Institute of Mental Health; Key Laboratory for Mental Health, Ministry of Health (Peking University); Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China.Department of Radiology, Peking University Third Hospital, Beijing, China.McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.Dementia Care & Research Center, Peking University Institute of Mental Health; Key Laboratory for Mental Health, Ministry of Health (Peking University); Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China.State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.Dementia Care & Research Center, Peking University Institute of Mental Health; Key Laboratory for Mental Health, Ministry of Health (Peking University); Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25624419

Citation

Wang, Xiao, et al. "Apolipoprotein E Ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 45, no. 3, 2015, pp. 781-95.
Wang X, Wang J, He Y, et al. Apolipoprotein E ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease. J Alzheimers Dis. 2015;45(3):781-95.
Wang, X., Wang, J., He, Y., Li, H., Yuan, H., Evans, A., Yu, X., He, Y., & Wang, H. (2015). Apolipoprotein E ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 45(3), 781-95. https://doi.org/10.3233/JAD-142556
Wang X, et al. Apolipoprotein E Ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease. J Alzheimers Dis. 2015;45(3):781-95. PubMed PMID: 25624419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease. AU - Wang,Xiao, AU - Wang,Jinhui, AU - He,Yi, AU - Li,Huiying, AU - Yuan,Huishu, AU - Evans,Alan, AU - Yu,Xin, AU - He,Yong, AU - Wang,Huali, PY - 2015/1/28/entrez PY - 2015/1/28/pubmed PY - 2016/1/20/medline KW - Apolipoprotein E KW - default-mode KW - functional connectivity KW - hippocampus KW - resting-state functional MRI SP - 781 EP - 95 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 45 IS - 3 N2 - The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD). Numerous studies have suggested that the modulation of APOE ε4 affects cognition and brain structure and function in healthy populations, particularly in the hippocampus, a key area associated with AD pathology. However, the effect of APOE ε4 allele on cognitive performance, hippocampal structural morphology, and specifically on functional characteristics in patients with AD remains poorly understood. Here, we employed a neuropsychological battery test and multi-modal structural MRI and resting-state functional MRI dataset to systematically investigate cognitive performance, hippocampal structural volume, and functional properties (including local low-frequency oscillating amplitude, intra-regional functional synchrony, and inter-regional functional connectivity) in 16 APOE ε4-carriers and 26 non-carriers at early stages of AD. Compared to non-carriers, APOE ε4-carriers exhibited poorer performance on recognition performance, but performed better on the late item generation of the verbal fluency task (associated with executive function). Structural imaging analysis revealed that APOE ε4-carriers exhibited smaller left hippocampal volumes compared to non-carriers, and the result remains significant after correcting for effects of brain size. Functional imaging analysis revealed that APOE ε4-carriers exhibited decreased amplitude of low-frequency fluctuations in the left hippocampus, non-significant changes in intra-regional synchronization within the hippocampus and decreased hippocampal functional connectivity predominantly in components of the default-mode network including the medial frontal and parietal cortices and the lateral temporal cortical regions. Taken together, our results showed APOE genotypic effects on the cognitive profile and hippocampal structural and functional characteristics in patients at early stages of AD, thus providing empirical evidence for the modulation of the APOE genotype on disease phenotype. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/25624419/Apolipoprotein_E_ε4_Modulates_Cognitive_Profiles_Hippocampal_Volume_and_Resting_State_Functional_Connectivity_in_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-142556 DB - PRIME DP - Unbound Medicine ER -