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Neuro-inflammation
Research paper
Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias
  1. Eleanor King,
  2. John Tiernan O’Brien,
  3. Paul Donaghy,
  4. Christopher Morris,
  5. Nicola Barnett,
  6. Kirsty Olsen,
  7. Carmen Martin-Ruiz,
  8. John-Paul Taylor,
  9. Alan J Thomas
  1. Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Dr Eleanor King, Institute of Neuroscience, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5P, UK; eleanor.king{at}newcastle.ac.uk

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.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/jnnp-2017-317134

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    Footnotes

    • Contributors EK contributed towards planning the study, analysing data and interpreting results, and writing the manuscript. JTOB contributed towards designing the study and drafting the manuscript. PD contributed towards acquiring data and drafting the manuscript. CM contributed towards designing the study and drafting the manuscript. NB contributed towards acquiring the data and drafting the manuscript. KO contributed towards acquiring the data and drafting the manuscript. CM-R contributed towards analysing the data and drafting the manuscript. JPT contributed towards acquiring data and drafting the manuscript. AT contributed towards design of the study, acquiring data, interpreting results and drafting the manuscript.

    • Funding We would like to acknowledge our funders: the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne NHS Foundation Trust and Newcastle University. Thanks to the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). EK is also grateful to the Royal College of Psychiatrists Pathfinder Fellowship for the grant that was provided for this project. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

    • Competing interests JTOB reports grants from Avid/Lilly during the conduct of the study. He also reports personal fees from GE Healthcare, personal fees from TauRx, grants and personal fees from Avid/Lilly, and personal fees from Axon, outside the submitted work. AT reports grants from NIHR BRU in Lewy Body Dementia and grants from Alzheimer’s Research UK during the conduct of the study. He also reports grants from GE Healthcare, outside the submitted work. All other authors have no further competing interests to declare.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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