APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article.
Yun Yan Su1, Xue Liang, U Joseph Schoepf
1From the Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nangjing, Jiangsu Province, China (YYS, XL, RQ, XK, HJC, GML, LJZ); and Division of Cardiovascular Imaging, Medical University of South Carolina, Ashley River Tower, Charleston, South Carolina (UJS, AV-S, HCW).
Apolipoprotein E (APOE) ε4 carriers show altered default mode network (DMN) functional connectivity in young adults. These DMN changes may indicate early genetic effects on the brain before structural or blood flow alterations.
Area of Science:
- Neuroimaging
- Genetics
- Cognitive Neuroscience
Background:
- The apolipoprotein E (APOE) gene is a significant genetic risk factor for various neurological disorders.
- Polymorphisms in the APOE gene, particularly the ε4 allele, are associated with altered brain structure and function.
- Understanding the early effects of APOE genotype on brain function in young, healthy adults is crucial for identifying potential biomarkers.
Purpose of the Study:
- To investigate the impact of APOE gene polymorphism on resting-state brain function, structure, and blood flow in healthy young adults.
- To determine if APOE genotype influences default mode network (DMN) functional connectivity (FC).
- To explore the relationship between brain parameters and cognitive performance.
Main Methods:
- Multimodality magnetic resonance (MR) imaging was employed in 76 healthy adults stratified by APOE genotype (ε4/ε3, ε3/ε3, ε2/ε3).
- Resting-state functional MRI was used to analyze DMN and amplitude of low-frequency fluctuations.
- Voxel-based morphometry, diffusion tensor imaging, and arterial spin labeling for cerebral blood flow were also performed.
Main Results:
- No significant differences were observed in neuropsychological tests, brain structure, or global cerebral blood flow across APOE genotype groups.
- APOE ε4/ε3 carriers exhibited increased DMN functional connectivity in the medial prefrontal cortex and posterior cingulate cortex/precuneus compared to ε3/ε3 carriers.
- Increased DMN FCs in the right temporal lobe positively correlated with vocabulary learning, delayed recall, and graph recall performance.
Conclusions:
- APOE ε4 carriers demonstrate significantly altered DMN functional connectivity compared to ε2 and ε3 carriers in cognitively intact young adults.
- APOE ε4 influences DMN functional connectivity prior to detectable changes in brain structure or blood flow.
- DMN functional connectivity may serve as an early biomarker for the genetic effects of APOE.
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