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

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Authors
Yi, Dahyun; Lee, Younghwa; Byun, Min Soo; Lee, Jun Ho; Ko, Kang; Sohn, Bo Kyung; Choe, Young Min; Choi, Hyo Jung; Baek, Hyewon; Sohn, Chul-Ho; Kim, Yu Kyeong; Lee, Dong Young
Issue Date
2018-08-23
Publisher
BioMed Central
Citation
Alzheimer's Research & Therapy, 10(1):84
Keywords
APOEFamily history of Alzheimer’s diseaseCognitively normal adultsAmyloid beta depositionCerebral glucose metabolism
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.
ISSN
1758-9193
Language
English
URI
https://doi.org/10.1186/s13195-018-0411-x

http://hdl.handle.net/10371/143540
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College of Medicine/School of Medicine (의과대학/대학원)Radiology (영상의학전공)Journal Papers (저널논문_영상의학전공)
College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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