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Close-range blast exposure is associated with altered white matter integrity in APOE ε4 carriers.

Abstract

Evidence suggests that blast exposure has profound negative consequences for the health of the human brain and that it may confer risk for the development of neurodegenerative diseases such as chronic traumatic encephalopathy and Alzheimer's disease (AD). Though the molecular mechanisms linking blast exposure to subsequent neurodegeneration is an active focus of research, recent studies suggest that genetic risk for AD may elevate the risk of neurodegeneration following traumatic brain injury (TBI). However, it is currently unknown if blast exposure also interacts with AD risk to promote neurodegeneration. In this study we examined whether apolipoprotein (APOE) ε4, a well-known genetic risk factor for AD, influenced the relationship between blast exposure and white matter integrity in a cohort of 200 Iraq and Afghanistan War veterans. Analyses revealed a significant interaction between close-range blast exposure (CBE; i.e., within 10 meters) and APOE ε4 carrier status in predicting white matter abnormalities, measured by a voxel-wise cluster-based method that captures spatial heterogeneity in white matter disruptions. This interaction remained significant after controlling for TBI, pointing to the specificity of CBE and APOE in white matter disruptions. Furthermore, among veteran ε4 carriers exposed to close-range blast, we observed a positive association between the number of CBEs and the number of white matter abnormalities. These results raise the possibility that CBE interacts with AD genetic influences on neuropathological processes such as the degradation of white matter integrity.

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  • Authors+Show Affiliations

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    National Center for PTSD, VA Boston Healthcare System , 150 S Huntington Ave (116B-2) , Boston, Massachusetts, United States , 02130. Boston University School of Medicine, Psychiatry ; danielle.sullivan2@va.gov.

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    National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts, United States. Boston University School of Medicine, Boston, Massachusetts, United States ; mark.logue@va.gov.

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    National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts, United States. Boston University School of Medicine, Psychiatry, Boston, Massachusetts, United States ; erika.wolf@va.gov.

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    National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts, United States. Boston University School of Medicine, Boston, Massachusetts, United States ; hayes.1075@osu.edu.

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    VA Boston Healthcare System, Neuroimaging Research for Veterans (NeRVe) Center, Boston, Massachusetts, United States. VA Boston Healthcare System, Translational Research Center for TBI and Stress Disorders (TRACTS), Boston, Massachusetts, United States. Athinoula A Martinos Center for Biomedical Imaging, 218916, Charlestown, Massachusetts, United States ; salat@nmr.mgh.harvard.edu.

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    VA Boston Healthcare System, Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), Boston, Massachusetts, United States. Harvard Medical School, 1811, Psychiatry, Boston, Massachusetts, United States ; Catherine.Fortier@va.gov.

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    VA Boston Healthcare System, Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), Boston, Massachusetts, United States. Boston University School of Medicine, Psychiatry, Boston, Massachusetts, United States. Harvard Medical School, 1811, Psychiatry, Boston, Massachusetts, United States ; Jennifer.Fonda@va.gov.

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    VA Boston Healthcare System, Translational Research Center for TBI and Stress Disorders (TRACTS), Boston, Massachusetts, United States. VA Boston Healthcare System, Geriatric Research, Education, and Clinical Center (GRECC), Boston, Massachusetts, United States. Harvard Medical School, Psychiatry, Boston, Massachusetts, United States ; Regina_McGlinchey@hms.harvard.edu.

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    Harvard Medical School, Psychiatry, Boston, Massachusetts, United States ; William_milberg@hms.harvard.edu.

    National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts, United States. Boston University School of Medicine, Psychiatry, Boston, Massachusetts, United States ; mark.miller5@va.gov.

    Source

    Journal of neurotrauma : 2019 Jun 22 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31232163

    Citation

    Sullivan, Danielle R., et al. "Close-range Blast Exposure Is Associated With Altered White Matter Integrity in APOE Ε4 Carriers." Journal of Neurotrauma, 2019.
    Sullivan DR, Logue M, Wolf EJ, et al. Close-range blast exposure is associated with altered white matter integrity in APOE ε4 carriers. J Neurotrauma. 2019.
    Sullivan, D. R., Logue, M., Wolf, E. J., Hayes, J. P., Salat, D., Fortier, C. B., ... Miller, M. W. (2019). Close-range blast exposure is associated with altered white matter integrity in APOE ε4 carriers. Journal of Neurotrauma, doi:10.1089/neu.2019.6489.
    Sullivan DR, et al. Close-range Blast Exposure Is Associated With Altered White Matter Integrity in APOE Ε4 Carriers. J Neurotrauma. 2019 Jun 22; PubMed PMID: 31232163.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Close-range blast exposure is associated with altered white matter integrity in APOE ε4 carriers. AU - Sullivan,Danielle R, AU - Logue,Mark, AU - Wolf,Erika J, AU - Hayes,Jasmeet P, AU - Salat,David, AU - Fortier,Catherine B, AU - Fonda,Jennifer R, AU - McGlinchey,Regina, AU - Milberg,William, AU - Miller,Mark W, Y1 - 2019/06/22/ PY - 2019/6/25/entrez KW - AXONAL INJURY KW - Diffusion Tensor Imaging KW - HEAD TRAUMA KW - NEURODEGENERATIVE DISORDERS JF - Journal of neurotrauma JO - J. Neurotrauma N2 - Evidence suggests that blast exposure has profound negative consequences for the health of the human brain and that it may confer risk for the development of neurodegenerative diseases such as chronic traumatic encephalopathy and Alzheimer's disease (AD). Though the molecular mechanisms linking blast exposure to subsequent neurodegeneration is an active focus of research, recent studies suggest that genetic risk for AD may elevate the risk of neurodegeneration following traumatic brain injury (TBI). However, it is currently unknown if blast exposure also interacts with AD risk to promote neurodegeneration. In this study we examined whether apolipoprotein (APOE) ε4, a well-known genetic risk factor for AD, influenced the relationship between blast exposure and white matter integrity in a cohort of 200 Iraq and Afghanistan War veterans. Analyses revealed a significant interaction between close-range blast exposure (CBE; i.e., within 10 meters) and APOE ε4 carrier status in predicting white matter abnormalities, measured by a voxel-wise cluster-based method that captures spatial heterogeneity in white matter disruptions. This interaction remained significant after controlling for TBI, pointing to the specificity of CBE and APOE in white matter disruptions. Furthermore, among veteran ε4 carriers exposed to close-range blast, we observed a positive association between the number of CBEs and the number of white matter abnormalities. These results raise the possibility that CBE interacts with AD genetic influences on neuropathological processes such as the degradation of white matter integrity. SN - 1557-9042 UR - https://www.unboundmedicine.com/medline/citation/31232163/Close-range_blast_exposure_is_associated_with_altered_white_matter_integrity_in_APOE_ε4_carriers L2 - https://www.liebertpub.com/doi/full/10.1089/neu.2019.6489?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -