Peripheral immunophenotype in dementia with Lewy bodies and Alzheimer's disease: an observational clinical study

J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1219-1226. doi: 10.1136/jnnp-2020-323603. Epub 2020 Sep 23.

Abstract

Background: Inflammation plays a key role in the aetiology and progression of Alzheimer's disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly. We hypothesised that, using blood biomarkers, DLB would show an increased proinflammatory profile compared with controls, and that there would be a distinct profile compared with AD.

Methods: 93 participants (31 with DLB, 31 with AD and 31 healthy older controls) completed a single study visit for neuropsychiatric testing and phlebotomy. Peripheral blood mononuclear cells were quantified for T and B cell subsets using flow cytometry, and serum cytokine concentrations were measured using multiplex immunoassay.

Results: We detected reduced relative numbers of helper T cells and reduced activation of B cells in DLB compared with AD. Additionally, interleukin (IL)-1β was detected more frequently in DLB and the serum concentration of IL-6 was increased compared with controls.

Conclusions: Peripheral inflammation is altered in DLB compared with AD, with T cell subset analysis supporting a possible shift towards senescence of the adaptive immune system in DLB. Furthermore, there is a proinflammatory signature of serum cytokines in DLB. Identification of this unique peripheral immunophenotype in DLB could guide development of an immune-based biomarker and direct future work exploring potential immune modulation as a novel treatment.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / physiopathology
  • B-Lymphocytes / immunology*
  • Case-Control Studies
  • Cytokines / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Immunoassay
  • Immunophenotyping
  • Interleukin-1beta / immunology*
  • Interleukin-6 / immunology*
  • Lewy Body Disease / immunology*
  • Lewy Body Disease / physiopathology
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Monocytes / immunology*
  • Neuropsychological Tests
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Cytokines
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6