Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease

Gabriel Westman, David Berglund, Johan Widén, Martin Ingelsson, Olle Korsgren, Lars Lannfelt, Dag Sehlin, Anna-Karin Lidehall, Britt-Marie Eriksson

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) has been associated with increased local inflammation in the affected brain regions, and in some studies also with elevated levels of proinflammatory cytokines in peripheral blood. Cytomegalovirus (CMV) is known to promote a more effector-oriented phenotype in the T-cell compartment, increasing with age. The aim of this study was to investigate the inflammatory response of peripheral blood mononuclear cells (PBMCs) from AD patients and non-demented (ND) controls. Using a multiplex Luminex xMAP assay targeting GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10 and TNF-α, cytokine profiles from PBMCs were analysed after stimulation with anti-CD3/CD28 beads, CMV pp65 peptide mix or amyloid β (Aβ) protofibrils, respectively. CMV seropositive AD subjects presented with higher IFN-γ levels after anti-CD3/CD28 and CMV pp65 but not after Aβ stimulation, compared to CMV seropositive ND controls. When analysing IFN-γ response to anti-CD3/CD28 stimulation on a subgroup level, CMV seropositive AD subjects presented with higher levels compared to both CMV seronegative AD and CMV seropositive ND subjects. Taken together, our data from patients with clinically manifest AD suggest a possible role of CMV as an inflammatory promoter in AD immunology. Further studies of AD patients at earlier stages of disease, could provide better insight into the pathophysiology.

Original languageEnglish
Article numbere96779
Number of pages9
JournalPLoS ONE
Volume9
Issue number5
DOIs
Publication statusPublished - 2014
Externally publishedYes

Subject classification (UKÄ)

  • Geriatrics
  • Immunology in the medical area
  • Neurology

Free keywords

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease/blood
  • Cytokines/blood
  • Cytomegalovirus/isolation & purification
  • Cytomegalovirus Infections/blood
  • Female
  • Humans
  • Inflammation/blood
  • Leukocytes, Mononuclear/immunology
  • Male

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