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Multiplex analyte assays to characterize different dementias: brain inflammatory cytokines in poststroke and other dementias

Lookup NU author(s): Dr Aiqing Chen, Arthur Oakley, Maria Monteiro, Katri Tuomela, Dr Louise Allan, Dr Elizabeta Mukaetova-Ladinska, Professor John O'Brien, Professor Raj KalariaORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Both the inflammatory potential and cognitive function decline during aging. The association between the repertoire of inflammatory biomarkers and cognitive decline is unclear. Inflammatory cytokines have been reported to be increased, decreased, or unchanged in the cerebrospinal fluid and sera of subjects with dementia. We assessed 112 postmortem brains from subjects diagnosed with poststroke dementia (PSD), vascular dementia, mixed dementia, and Alzheimer's disease (AD), comparing those to poststroke nondemented (PSND) subjects and age-matched controls. We analyzed 5 brain regions including the gray and white matter from the frontal and temporal lobes for a panel of cytokine and/or chemokine analytes using multiplex-array assays. Of the 37 analytes, 14 were under or near the detection limits, 7 were close to the lowest detection level, and 16 cytokines were within the linear range of the assay. We observed widely variable concentrations of C-reactive protein (CRP) and serum amyloid A at the high end (1-150 ng/mg protein), whereas several of the interleukins (IL, interferon-gamma and tumor necrosis factor) at the low end (1-10 pg/mg). There were also regional variations; most notable being high concentrations of some cytokines (e.g., CRP and angiogenesis panel) in the frontal white matter. Overall, we found decreased concentrations of several cytokines, including IL-1 beta (p = 0.000), IL-6 (p = 0.000), IL-7 (p = 0.000), IL-8 (p = 0.000), IL-16 (p = 0.001), interferon-inducible proteine10 (0.044), serum amyloid A (p = 0.011), and a trend in IL-1 alpha (p = 0.084) across all dementia groups compared to nondemented controls. IL-6 and IL-8 were significantly lower in dementia subjects than in nondemented subjects in every region. In particular, lower levels of IL-6 and IL-8 were notable in the PSD compared to PSND subjects. Because these 2 stroke groups had comparable degree of vascular pathology, the lower production of IL-6 and IL-8 in PSD reaffirms a possible specific involvement of immunosenescence in dementia pathogenesis. In contrast, CRP was not altered between dementia and nondementia subjects or between PSD and PSND. Our study provides evidence not only for the feasibility of tracking cytokines in postmortem brain tissue but also suggests differentially impaired inflammatory mechanisms underlying dementia including AD. There was a diminished inflammatory response, possibly reflecting immunosenescence and cerebral atrophy, in all dementias. Strategies to enhance anti-inflammatory cytokines and boost the immune system of the brain may be beneficial for preventing cognitive dysfunction, especially after stroke. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.

Publication metadata

Author(s): Chen AQ, Oakley AE, Monteiro M, Tuomela K, Allan LM, Mukaetova-Ladinska EB, O'Brien JT, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2016

Volume: 38

Pages: 56-67

Print publication date: 01/02/2016

Online publication date: 30/10/2015

Acceptance date: 24/10/2015

Date deposited: 01/03/2016

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier


DOI: 10.1016/j.neurobiolaging.2015.10.021


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Funder referenceFunder name
Alzheimer's Research (ARUK)
Alzheimer's Society and ARUK as part of the Brains for Dementia Research Project
Meso-Scale Discovery (MSD)
Newcastle Centre for Brain Ageing and Vitality (BBSRC)
Newcastle Centre for Brain Ageing and Vitality (EPSRC)
Newcastle Centre for Brain Ageing and Vitality (ESRC)
Newcastle Centre for Brain Ageing and Vitality (MRC, LLHW)
Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases award
G0400074UK MRC
G0500247Medical Research Council (MRC)
R277/0213Dunhill Medical Trust UK