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Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE ε4

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Abstract

In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.

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Abbreviations

AD:

Alzheimer’s disease

APOE :

apolipoprotein E

APP :

amyloid precursor protein

DMN:

default mode network

FC:

functional connectivity

MCC:

middle cingulate cortices

PCC:

posterior cingulate cortex

PCu:

precuneus

rs-fMRI:

resting-state functional MR imaging

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Authors and Affiliations

  1. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China

    Yun Yan Su, Xiao Dong Zhang, Xue Liang, Li Juan Zheng, Gang Zheng, Xiang Kong, Qiang Xu, Shou Ju Wang, Rong Feng Qi, Guang Ming Lu & Long Jiang Zhang

  2. College of Civil Aviation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, 210016, China

    Gang Zheng

  3. Division of Cardiovascular Imaging, Medical University of South Carolina Ashley River Tower, MSC 226, 25 Courtenay Dr, Charleston, SC, 29425, USA

    U. Joseph Schoepf, Akos Varga-Szemes & Andrew Stubenrauch

Authors
  1. Yun Yan Su
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  2. Xiao Dong Zhang
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  3. U. Joseph Schoepf
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  4. Akos Varga-Szemes
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  5. Andrew Stubenrauch
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  6. Xue Liang
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  7. Li Juan Zheng
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  8. Gang Zheng
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  9. Xiang Kong
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  10. Qiang Xu
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  11. Shou Ju Wang
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  12. Rong Feng Qi
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  13. Guang Ming Lu
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  14. Long Jiang Zhang
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Corresponding authors

Correspondence to Guang Ming Lu or Long Jiang Zhang.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the local Medical Research Ethics Committee of Jinling Hospital (China).

Funding

This study was funded by the grants from Natural Scientific Foundation of China (81,322,020, 81,230,032, and 81,171,313 to L.J.Z.) and Program for New Century Excellent Talents in University (NCET-12-0260 to L.J.Z.).

Competing financial interests

Dr. Schoepf is a consultant for and receives research support from Astellas, Bayer, Bracco, GE, Medrad, and Siemens. The other authors have no conflict of interest to disclose.

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Su, Y.Y., Zhang, X.D., Schoepf, U.J. et al. Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE ε4 . Brain Imaging and Behavior 11, 818–828 (2017). https://doi.org/10.1007/s11682-016-9556-z

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