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Alzheimers Res Ther. 2018 Aug 23;10(1):84. doi: 10.1186/s13195-018-0411-x.

Synergistic interaction between APOE and family history of Alzheimer's disease on cerebral amyloid deposition and glucose metabolism.

Author information

1
Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.
2
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
3
Department of Psychiatry, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea.
4
Department of Neuropsychiatry, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
5
Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.
6
Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Yongin, Republic of Korea.
7
Department of Radiology, Seoul National University College of Medicine & Seoul National University Hospital, Seoul, Republic of Korea.
8
Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.
9
Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea. selfpsy@snu.ac.kr.
10
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea. selfpsy@snu.ac.kr.
11
Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. selfpsy@snu.ac.kr.

Abstract

BACKGROUND:

Recently, the field of gene-gene or gene-environment interaction research appears to have gained growing interest, although it is seldom investigated in Alzheimer's disease (AD). Hence, the current study aims to investigate interaction effects of the key genetic and environmental risks-the apolipoprotein ε4 allele (APOE4) and family history of late-onset AD (FH)-on AD-related brain changes in cognitively normal (CN) middle-aged and older adults.

METHODS:

[11C] Pittsburg compound-B (PiB) positron emission tomography (PET) imaging as well as [18F] fluoro-2-deoxyglucose (FDG) PET that were simultaneously taken with T1-weighted magnetic resonance imaging (MRI) were obtained from 268 CNs from the Korean Brain Aging Study for Early Diagnosis and Prediction of AD (KBASE). Composite standardized uptake value ratios were obtained from PiB-PET and FDG-PET images in the AD signature regions of interests (ROIs) and analyzed. Voxel-wise analyses were also performed to examine detailed regional changes not captured by the ROI analyses.

RESULTS:

A significant synergistic interaction effect was found between the APOE4 and FH on amyloid-beta (Aβ) deposition in the AD signature ROIs as well as other regions. Synergistic interaction effects on cerebral glucose metabolism were observed in the regions not captured by the AD signature ROIs, particularly in the medial temporal regions.

CONCLUSIONS:

Strong synergistic effects of APOE4 and FH on Aβ deposition and cerebral glucose metabolism in CN adults indicate possible gene-to-gene or gene-to-environment interactions that are crucial for pathogenesis of AD involving Aβ. Other unspecified risk factors-genes and/or environmental-that are captured by the positive FH status might either coexpress or interact with APOE4 to alter AD-related brain changes in CN. Healthy people with both FH and APOE4 need more attention for AD prevention.

KEYWORDS:

APOE; Amyloid beta deposition; Cerebral glucose metabolism; Cognitively normal adults; Family history of Alzheimer’s disease

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