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Close-Range Blast Exposure Is Associated with Altered White Matter Integrity in Apolipoprotein ɛ4 Carriers.
J Neurotrauma. 2019 Dec 01; 36(23):3264-3273.JN

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). Although 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) ɛ4, 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) (close range being within 10 m) and APOE ɛ4 carrier status in predicting white matter abnormalities, measured by a voxelwise 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. Further, among veteran ɛ4 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.

Authors+Show Affiliations

National Center for PTSD, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.National Center for PTSD, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.National Center for PTSD, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.National Center for PTSD, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts. Neuroimaging Research for Veterans Center, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychology, The Ohio State University, Columbus, Ohio.Neuroimaging Research for Veterans Center, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Anthinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts. Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.National Center for PTSD, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.

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 Apolipoprotein Ɛ4 Carriers." Journal of Neurotrauma, vol. 36, no. 23, 2019, pp. 3264-3273.
Sullivan DR, Logue MW, Wolf EJ, et al. Close-Range Blast Exposure Is Associated with Altered White Matter Integrity in Apolipoprotein ɛ4 Carriers. J Neurotrauma. 2019;36(23):3264-3273.
Sullivan, D. R., Logue, M. W., Wolf, E. J., Hayes, J. P., Salat, D. H., Fortier, C. B., Fonda, J. R., McGlinchey, R. E., Milberg, W. P., & Miller, M. W. (2019). Close-Range Blast Exposure Is Associated with Altered White Matter Integrity in Apolipoprotein ɛ4 Carriers. Journal of Neurotrauma, 36(23), 3264-3273. https://doi.org/10.1089/neu.2019.6489
Sullivan DR, et al. Close-Range Blast Exposure Is Associated With Altered White Matter Integrity in Apolipoprotein Ɛ4 Carriers. J Neurotrauma. 2019 Dec 1;36(23):3264-3273. 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 Apolipoprotein ɛ4 Carriers. AU - Sullivan,Danielle R, AU - Logue,Mark W, AU - Wolf,Erika J, AU - Hayes,Jasmeet P, AU - Salat,David H, AU - Fortier,Catherine B, AU - Fonda,Jennifer R, AU - McGlinchey,Regina E, AU - Milberg,William P, AU - Miller,Mark W, Y1 - 2019/08/01/ PY - 2019/6/25/pubmed PY - 2019/6/25/medline PY - 2019/6/25/entrez KW - AD KW - APOE KW - blast KW - diffusion tensor imaging KW - white matter SP - 3264 EP - 3273 JF - Journal of neurotrauma JO - J. Neurotrauma VL - 36 IS - 23 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). Although 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) ɛ4, 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) (close range being within 10 m) and APOE ɛ4 carrier status in predicting white matter abnormalities, measured by a voxelwise 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. Further, among veteran ɛ4 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 -
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