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Apolipoprotein E: the resilience gene

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Abstract

The apolipoprotein E (apoE) gene has been implicated in various conditions, most notably Alzheimer’s disease and coronary artery disease. A predisposing role of the apoE4 isoform and a protective role of apoE2 isoform in those diseases have been documented. Here we investigated the role of apoE in resilience to trauma. Three hundred and forty-three US veterans were genotyped for apoE and were assessed for their lifetime trauma exposure (trauma score, T) and severity of posttraumatic stress disorder symptoms (PCL). The ratio PCL/T indicates sensitivity to trauma; hence, its inverse indicates resilience, R, to trauma. We found a significantly higher resilience in participants with apoE genotype containing the E2 allele (E2/2, E2/3) as compared to participants with the E4 allele (E4/4, E4/3). In addition, when the categorical apoE genotype was reexpressed as the number of cysteine residues per apoE mole (CysR/mole), a highly significant positive association was found between resilience and CysR/mole, such that resilience was systematically higher as the number of CysR/mole increased, from zero CysR/mole in E4/4 to four CysR/mole in E2/2. These findings demonstrate the protective role of the CysR/mole apoE in resilience to trauma: the more CysR/mole, the higher the resilience. Thus, they are in accord with other findings pointing to a generally protective role of increasing number of CysR/mole (from E4/4 to E2/2) in other diseases. However, unlike other conditions (e.g., Alzheimer’s disease and coronary artery disease), resilience to trauma is not a disease but an adaptive response to trauma. Therefore, the effects of apoE seem to be more pervasive along the CysR/mole continuum, most probably reflecting underlying effects on brain synchronicity and its variability that we have documented previously (Leuthold et al., Exp Brain Res 226:525–536, 2013).

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Acknowledgements

This study was supported in part by the US Department of Veterans Affairs and the University of Minnesota. The contents of this paper do not represent the views of the US Department of Veterans Affairs or the United States Government.

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Authors and Affiliations

  1. Department of Veterans Affairs Health Care System, Brain Sciences Center (11B), Minneapolis VAHCS, One Veterans Drive, Minneapolis, MN, 55417, USA

    Lisa M. James, Brian E. Engdahl & Apostolos P. Georgopoulos

  2. Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Lisa M. James, Brian E. Engdahl & Apostolos P. Georgopoulos

  3. Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Lisa M. James & Apostolos P. Georgopoulos

  4. Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, USA

    Lisa M. James, Brian E. Engdahl & Apostolos P. Georgopoulos

  5. Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA

    Brian E. Engdahl

  6. Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Apostolos P. Georgopoulos

Authors
  1. Lisa M. James
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  2. Brian E. Engdahl
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  3. Apostolos P. Georgopoulos
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Correspondence to Lisa M. James.

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James, L.M., Engdahl, B.E. & Georgopoulos, A.P. Apolipoprotein E: the resilience gene. Exp Brain Res 235, 1853–1859 (2017). https://doi.org/10.1007/s00221-017-4941-4

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  • DOI: https://doi.org/10.1007/s00221-017-4941-4

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