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Genetics pathway-based imaging approaches in Chinese Han population with Alzheimer’s disease risk

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Abstract

The tau hypothesis has been raised with regard to the pathophysiology of Alzheimer’s disease (AD). Mild cognitive impairment (MCI) is associated with a high risk for developing AD. However, no study has directly examined the brain topological alterations based on combined effects of tau protein pathway genes in MCI population. Forty-three patients with MCI and 30 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) in Chinese Han, and a tau protein pathway-based imaging approaches (7 candidate genes: 17 SNPs) were used to investigate changes in the topological organisation of brain activation associated with MCI. Impaired regional activation is related to tau protein pathway genes (5/7 candidate genes) in patients with MCI and likely in topologically convergent and divergent functional alterations patterns associated with genes, and combined effects of tau protein pathway genes disrupt the topological architecture of cortico-cerebellar loops. The associations between the loops and behaviours further suggest that tau protein pathway genes do play a significant role in non-episodic memory impairment. Tau pathway-based imaging approaches might strengthen the credibility in imaging genetic associations and generate pathway frameworks that might provide powerful new insights into the neural mechanisms that underlie MCI.

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Acknowledgments

Thanks to all participants. This research was partly supported by the National Natural Science Foundation of China (No. 81201080, 91332104); Program for New Century Excellent Talents in University (No. NCET-13-0117); Key Program for Clinical Medicine and Science and Tochnology: Jiangsu Provence Clinical Medical Research Center (No.BL2013025); Natural Science Foundation of Jiangsu Province (No. BK2012337) and Doctoral Fund of Ministry of Education of China (20120092120068). None of the authors have a conflict of interest, financial or otherwise, directly or indirectly related to this work.

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Authors and Affiliations

  1. Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, The Institute of Neuropsychiatry of Southeast University, Nanjing, 210009, China

    Feng Bai, Yongmei Shi, Yonggui Yuan & Zhijun Zhang

  2. Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, 310015, China

    Wei Liao

  3. Medical School of Southeast University, Nanjing, 210009, China

    Chunxian Yue, Mengjia Pu, Hui Yu & Leiyu Geng

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  1. Feng Bai
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  2. Wei Liao
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  3. Chunxian Yue
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  4. Mengjia Pu
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  5. Yongmei Shi
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  6. Hui Yu
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  7. Yonggui Yuan
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  8. Leiyu Geng
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  9. Zhijun Zhang
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Correspondence to Feng Bai or Zhijun Zhang.

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F. Bai and W. Liao contributed equally to this work.

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Bai, F., Liao, W., Yue, C. et al. Genetics pathway-based imaging approaches in Chinese Han population with Alzheimer’s disease risk. Brain Struct Funct 221, 433–446 (2016). https://doi.org/10.1007/s00429-014-0916-4

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