Brain Imaging and Behavior

, Volume 11, Issue 3, pp 818–828 | Cite as

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

  • Yun Yan Su
  • Xiao Dong Zhang
  • U. Joseph Schoepf
  • Akos Varga-Szemes
  • Andrew Stubenrauch
  • Xue Liang
  • Li Juan Zheng
  • Gang Zheng
  • Xiang Kong
  • Qiang Xu
  • Shou Ju Wang
  • Rong Feng Qi
  • Guang Ming LuEmail author
  • Long Jiang ZhangEmail author
Original Research


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.


Default-mode network Apolipoprotein E Amyloid precursor protein Presenilin-1 Presenilin-2 Alzheimer’s disease 



Alzheimer’s disease


apolipoprotein E


amyloid precursor protein


default mode network


functional connectivity


middle cingulate cortices


posterior cingulate cortex




resting-state functional MR imaging


Compliance with ethical standards

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).


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.

Supplementary material

11682_2016_9556_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 18 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yun Yan Su
    • 1
  • Xiao Dong Zhang
    • 1
  • U. Joseph Schoepf
    • 3
  • Akos Varga-Szemes
    • 3
  • Andrew Stubenrauch
    • 3
  • Xue Liang
    • 1
  • Li Juan Zheng
    • 1
  • Gang Zheng
    • 1
    • 2
  • Xiang Kong
    • 1
  • Qiang Xu
    • 1
  • Shou Ju Wang
    • 1
  • Rong Feng Qi
    • 1
  • Guang Ming Lu
    • 1
    Email author
  • Long Jiang Zhang
    • 1
    Email author
  1. 1.Department of Medical Imaging, Jinling HospitalMedical School of Nanjing UniversityNangjingChina
  2. 2.College of Civil AviationNanjing University of Aeronautics and AstronauticsNanjingChina
  3. 3.Division of Cardiovascular ImagingMedical University of South Carolina Ashley River TowerCharlestonUSA

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