Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?
Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease. However, it is unknown whether rs405509 T allele synergizes with the APOE ε4 allele in influencing cognition and brain structure.



We analyzed the interaction effect of the rs405509 T allele and the APOE ε4 allele on cognitive ability and brain gray matter volume among elderly people. The subjects were grouped into four groups according to APOE and rs405509 genotypes.



Significant interaction effects were found between rs405509 and APOE on general mental status, memory and attention. Analysis of the whole brain gray matter showed a significantly positive interaction effect between rs405509and APOE on the right inferior temporal gyrus and right fusiform gyrus (alphasim correction P < 0.001). In addition, there was a significant relationship between cognitive ability and gray matter volume.



The data indicate that the APOE rs405509 T homozygote modulates the effect of APOE ε4 on both cognitive performance and brain gray matter structure.
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Ma
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Zhang
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Li
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Zhang
Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.|Banner Alzheimer's Institute, Phoenix, AZ, USA.
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Chen
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Liang
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Chen
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Liu
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.|Beijing Ageing Brain Rejuvenation Initiative Centre, Beijing Normal University, Beijing, China.
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Zhang
D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People; D001288:Attention; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D000073216:Mental Status and Dementia Tests; D013702:Temporal Lobe / Q000473:pathology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E
Alzheimer's disease; apolipoprotein E; cognitive impairment; interaction; magnetic resonance imaging; risk factor; rs405509; voxel-based morphometry