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Research paper
APOE genotype and neuroimaging markers of Alzheimer's disease: systematic review and meta-analysis
  1. Ying Liu1,
  2. Jin-Tai Yu1,2,3,
  3. Hui-Fu Wang3,
  4. Pei-Ran Han4,
  5. Chen-Chen Tan2,
  6. Chong Wang2,
  7. Xiang-Fei Meng2,
  8. Shannon L Risacher5,
  9. Andrew J Saykin5,
  10. Lan Tan1,2,3
  1. 1Department of Neurology, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China
  2. 2Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China
  3. 3Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China
  4. 4Department of Cardiology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China
  5. 5Department of Radiology and Imaging Sciences, Center for Neuroimaging, School of Medicine, Indiana University, Indianapolis, Indiana, USA
  1. Correspondence to Dr Jin-Tai Yu, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China; yu-jintai{at}


Objective We aimed to examine the association of apolipoprotein E (APOE) ɛ4 genotype with neuroimaging markers of Alzheimer's disease: hippocampal volume, brain amyloid deposition and cerebral metabolism.

Methods We performed a systematic review and meta-analysis of 14 cross-sectional studies identified in Pubmed from 1996 to 2014 (n=1628). The pooled standard mean difference (SMD) was used to estimate the association between APOE and hippocampal volume and amyloid deposition. Meta-analysis was performed using effect size signed differential mapping using coordinates extracted from clusters with statistically significant difference in cerebral metabolic rate for glucose between APOE ɛ4+ and ɛ4− groups.

Results APOE ɛ4 carrier status was associated with atrophic hippocampal volume (pooled SMD: −0.47; 95% CI −0.82 to −0.13; p=0.007) and increased cerebral amyloid positron emission tomography tracer (pooled SMD: 0.62, 95% CI 0.27 to 0.98, p=0.0006). APOE ɛ4 was also associated with decreased cerebral metabolism, especially in right middle frontal gyrus.

Conclusions APOE ɛ4 was associated with atrophic hippocampal volume in MRI markers, increased cerebral amyloid deposition and cerebral hypometabolism. Theses associations may indicate the potential role of the APOE gene in the pathophysiology of Alzheimer's disease.

  • Alzheimer's disease
  • Apolipoprotein E
  • meta-analysis
  • hippocampal volume
  • amyloid deposition
  • hypometabolism

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