Apolipoprotein E (APOE) ε4 moderates the relationship between c-reactive protein, cognitive functioning, and white matter integrity.

Autor: Wooten T; Tufts University, Boston, MA, USA; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Boston Attention and Learning Laboratory, VA Healthcare System, Boston, MA, USA. Electronic address: thomas.wooten@tufts.edu., Brown E; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, MA, USA., Sullivan DR; National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA., Logue MW; National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Fortier CB; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Fonda JR; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., DeGutis J; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Boston Attention and Learning Laboratory, VA Healthcare System, Boston, MA, USA., Salat DH; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA., McGlinchey R; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Milberg W; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Esterman M; National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Boston Attention and Learning Laboratory, VA Healthcare System, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2021 Jul; Vol. 95, pp. 84-95. Date of Electronic Publication: 2021 Feb 23.
DOI: 10.1016/j.bbi.2021.02.016
Abstrakt: Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle-aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (β = -0.633), executive functioning (β = -0.566), and global fractional anisotropy (β = -0.470), such that elevated CRP was associated with worse cognition and white matter integrity in APOE ε4 carriers. Diffusion tensor imaging (DTI) was used to determine if CRP × APOE ε4 presence was associated with regionally specific fractional anisotropy in white matter tracts. Tract-based spatial statistics revealed CRP × APOE ε4 presence was associated with fractional anisotropy in the corpus callosum, right superior longitudinal fasciculus, right posterior corona radiata, as well as the bilateral anterior and superior corona radiatas. This suggests that APOE ε4 carriers may be uniquely vulnerable to the potentially negative impact of elevated systematic inflammation to cognition and microstructural white matter integrity.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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