APOE genotype and neuroimaging markers of Alzheimer's disease: systematic review and meta-analysis.
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.
Department of Neurology, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China.
Ying
Y
Liu
Department of Neurology, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Jin-Tai
JT
Yu
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Hui-Fu
HF
Wang
Department of Cardiology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China.
Pei-Ran
PR
Han
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Chen-Chen
CC
Tan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Chong
C
Wang
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Xiang-Fei
XF
Meng
Department of Radiology and Imaging Sciences, Center for Neuroimaging, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Shannon L
SL
Risacher
Department of Radiology and Imaging Sciences, Center for Neuroimaging, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Andrew J
AJ
Saykin
Department of Neurology, Dalian Medical University, Qingdao Municipal Hospital, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Lan
L
Tan
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers; D002540:Cerebral Cortex / Q000378:metabolism; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D059906:Neuroimaging
D000682:Amyloid; D053327:Apolipoprotein E4; D015415:Biomarkers; D005947:Glucose
Alzheimer's disease; Apolipoprotein E; amyloid deposition; hippocampal volume; hypometabolism; meta-analysis