Synergistic Effects of APOE and CLU May Increase the Risk of Alzheimer’s Disease: Acceleration of Atrophy in the Volumes and Shapes of the Hippocampus and Amygdala
Affiliations: [a]
School of Information Science and Engineering, Lanzhou University, Lanzhou, Gansu Province, China
| [b] Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| [c]
CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| [d]
Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
Correspondence:
[*]
Correspondence to: Dr. Zhijun Yao, School of Information Science and Engineering, Lanzhou University, P.O. Box 730000, Lanzhou, Gansu Province, China. Tel.: +86 186 9311 0998; E-mail: yaozj@lzu.edu.cn and Dr. Bin Hu, School of Information Science and Engineering, Lanzhou University, P.O. Box 730000, Lanzhou, Gansu Province, China. Tel.: +860931 8912 779; Fax: +860931 8912 779; E-mail: bh@lzu.edu.cn.
Note: [1] Data used in preparation for this article were obtained fromthe Alzheimer’s Disease Neuroimaging Initiative (ADNI) data-base (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNIand/or provided data but did not participate in the analysis or wri-ting of this report. A complete listing of ADNI investigators canbe found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Abstract: Background:The volume loss of the hippocampus and amygdala in non-demented individuals has been reported to increase the risk of developing Alzheimer’s disease (AD). Many neuroimaging genetics studies mainly focused on the individual effects of APOE and CLU on neuroimaging to understand their neural mechanisms, whereas their synergistic effects have been rarely studied. Objective:To assess whether APOE and CLU have synergetic effects, we investigated the epistatic interaction and combined effects of the two genetic variants on morphological degeneration of hippocampus and amygdala in the non-demented elderly at baseline and 2-year follow-up. Methods:Besides the widely-used volume indicator, the surface-based morphometry method was also adopted in this study to evaluate shape alterations. Results:Our results showed a synergistic effect of homozygosity for the CLU risk allele C in rs11136000 and APOE ɛ4 on the hippocampal and amygdalar volumes during a 2-year follow-up. Moreover, the combined effects of APOE ɛ4 and CLU C were stronger than either of the individual effects in the atrophy progress of the amygdala. Conclusion:These findings indicate that brain morphological changes are caused by more than one gene variant, which may help us to better understand the complex endogenous mechanism of AD.
