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Functional connectivity among brain regions affected in Alzheimer's disease is associated with CSF TNF-α in APOE4 carriers.

Abstract
It is now recognized that understanding how neuroinflammation affects brain function may provide new insights into Alzheimer's pathophysiology. Tumor necrosis factor (TNF)-α, an inflammatory cytokine marker, has been implicated in Alzheimer's disease (AD), as it can impair neuronal function through suppression of long-term potentiation. Our study investigated the relationship between cerebrospinal fluid TNF-α and functional connectivity (FC) in a cohort of 64 older adults (μ age = 69.76 years; 30 cognitively normal, 34 mild AD). Higher cerebrospinal fluid TNF-α levels were associated with lower FC among brain regions important for high-level decision-making, inhibitory control, and memory. This effect was moderated by apolipoprotein E-ε4 (APOE4) status. Graph theory metrics revealed there were significant differences between APOE4 carriers at the node level, and by diagnosis at the network level suggesting global brain network dysfunction in participants with AD. These findings suggest proinflammatory mechanisms may contribute to reduced FC in regions important for high-level cognition. Future studies are needed to understand the role of inflammation on brain function and clinical progression, especially in APOE4 carriers.
AuthorsJoey Annette Contreras, Vahan Aslanyan, Melanie D Sweeney, Lianne M J Sanders, Abhay P Sagare, Berislav V Zlokovic, Arthur W Toga, S Duke Han, John C Morris, Anne Fagan, Parinaz Massoumzadeh, Tammie L Benzinger, Judy Pa
JournalNeurobiology of aging (Neurobiol Aging) Vol. 86 Pg. 112-122 (02 2020) ISSN: 1558-1497 [Electronic] United States
PMID31870643 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Apolipoprotein E4
  • Tumor Necrosis Factor-alpha
Topics
  • Aged
  • Alzheimer Disease (cerebrospinal fluid, diagnostic imaging, genetics, physiopathology)
  • Apolipoprotein E4
  • Brain (diagnostic imaging, physiopathology)
  • Executive Function
  • Female
  • Heterozygote
  • Humans
  • Inflammation
  • Magnetic Resonance Imaging
  • Male
  • Tumor Necrosis Factor-alpha (cerebrospinal fluid)

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