Peripheral inflammation in prodromal Alzheimer's and Lewy body dementias

J Neurol Neurosurg Psychiatry. 2018 Apr;89(4):339-345. doi: 10.1136/jnnp-2017-317134. Epub 2017 Dec 16.

Abstract

Objectives: There is growing evidence for the role of systemic inflammation in Alzheimer's disease (AD) and other neurodegenerative diseases; however the systemic inflammatory profile in dementia with Lewy bodies (DLB) has never before been investigated. This study aimed to characterise systemic inflammatory mediators in established DLB and AD, as well as in their prodromal, mild cognitive impairment (MCI) phases.

Methods: We obtained plasma samples from patients with DLB (n=37), AD (n=20), MCI with DLB profile (n=38), MCI with AD profile (n=20) and healthy control subjects (n=20). The following inflammatory biomarkers were measured using Roche cobas c702 and Meso Scale Discovery V-Plex Plus: high-sensitivity C-reactive protein, interferon-gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL-2, IL-4, IL-6, IL-8 and tumour necrosis factor-alpha.

Results: We found significantly higher levels of IL-10, IL-1beta, IL-4 and IL-2 in both MCI groups (P<0.001), while there was no significant difference in inflammatory markers between dementia groups and controls. Furthermore, increased disease severity was associated with lower levels of IL-1beta, IL-2 and IL-4 (P<0.05).

Interpretation: We have shown for the first time that in both DLB and AD, increased peripheral inflammation occurs early at the MCI disease stages. These data support a role for inflammation early in the disease process, and have important implications for the stage of disease where trials of anti-inflammatory medication should be focused.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / immunology*
  • C-Reactive Protein / immunology*
  • Case-Control Studies
  • Cognitive Dysfunction / immunology*
  • Cytokines / immunology*
  • Female
  • Humans
  • Inflammation / immunology*
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-12 / immunology
  • Interleukin-13 / immunology
  • Interleukin-1beta / immunology
  • Interleukin-2 / immunology
  • Interleukin-4 / immunology
  • Interleukin-6 / immunology
  • Interleukin-8 / immunology
  • Lewy Body Disease / immunology*
  • Male
  • Prodromal Symptoms*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • CXCL8 protein, human
  • Cytokines
  • IL10 protein, human
  • IL1B protein, human
  • IL2 protein, human
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-13
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Interleukin-8
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • C-Reactive Protein