Neuroinflammation in comorbid depression in Alzheimer’s disease: a pilot study using post-mortem brain tissue
Neuroinflammation in comorbid depression in Alzheimer’s disease: a pilot study using post-mortem brain tissue
Background: comorbid depression and Alzheimer’s disease (AD) is associated with poorer prognosis than either condition alone. Neuroinflammation has been implicated in the pathogenesis and progression of both depression and AD, but much of the existing research has been based on peripheral blood immune markers. Relatively little is known about the neuroinflammatory environment when these conditions occur simultaneously and using immune measures directly in the brain tissue. This pilot study aims to examine brain inflammatory marker changes in AD cases comparing those with and without comorbid depression.
Methods: post-mortem brain tissue from AD cases with depression (n=23) and AD cases with no history of psychiatric illness (n=25) were analyzed for a range of inflammatory markers, including markers of microglial function (Iba1, P2RY12, CD64 and CD68 measured by immunohistochemistry); endothelial inflammatory markers (ICAM-1 and VCAM-1 measured by ELISA); and cytokine levels (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α measured using Mesoscale Discovery Multiplex Assays).
Results: brains of AD cases with comorbid depression, compared with AD alone, had increased IL-4 in the superior frontal gyrus and increased TNFα & IL-12p70 in the insula. Levels of all other inflammatory markers including markers of microglial function and endothelial inflammation were similar between the two groups.
Conclusion: we found no consistent changes in cytokines between the two brain regions in individuals with comorbid depression in AD. Further work in larger cohorts is needed to understand brain region specificity of immune marker alterations and the relationship of these changes with pre-mortem clinical outcomes.
Lin, Jordan T.
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Morisaki, Mizuki
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Sampathkumar, Srisharnitha A.
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Lau, Laurie C.
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Boche, Delphine
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Khandaker, Golam M.
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Sinclair, Lindsey I.
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Lin, Jordan T.
c8c57365-fc07-4e5e-91a3-80bd3fa18cda
Morisaki, Mizuki
40782647-ec82-47dd-8d33-13ea07e032b7
Sampathkumar, Srisharnitha A.
262b7904-fd86-4ce6-bd16-e58d14c1c0b0
Lau, Laurie C.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Khandaker, Golam M.
f6996233-5e6a-43a2-aa3e-0c438de3913e
Sinclair, Lindsey I.
badafe71-0df0-437e-ad73-4326450fed4c
Lin, Jordan T., Morisaki, Mizuki, Sampathkumar, Srisharnitha A., Lau, Laurie C., Boche, Delphine, Khandaker, Golam M. and Sinclair, Lindsey I.
(2024)
Neuroinflammation in comorbid depression in Alzheimer’s disease: a pilot study using post-mortem brain tissue.
Neuroscience Applied.
(In Press)
Abstract
Background: comorbid depression and Alzheimer’s disease (AD) is associated with poorer prognosis than either condition alone. Neuroinflammation has been implicated in the pathogenesis and progression of both depression and AD, but much of the existing research has been based on peripheral blood immune markers. Relatively little is known about the neuroinflammatory environment when these conditions occur simultaneously and using immune measures directly in the brain tissue. This pilot study aims to examine brain inflammatory marker changes in AD cases comparing those with and without comorbid depression.
Methods: post-mortem brain tissue from AD cases with depression (n=23) and AD cases with no history of psychiatric illness (n=25) were analyzed for a range of inflammatory markers, including markers of microglial function (Iba1, P2RY12, CD64 and CD68 measured by immunohistochemistry); endothelial inflammatory markers (ICAM-1 and VCAM-1 measured by ELISA); and cytokine levels (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α measured using Mesoscale Discovery Multiplex Assays).
Results: brains of AD cases with comorbid depression, compared with AD alone, had increased IL-4 in the superior frontal gyrus and increased TNFα & IL-12p70 in the insula. Levels of all other inflammatory markers including markers of microglial function and endothelial inflammation were similar between the two groups.
Conclusion: we found no consistent changes in cytokines between the two brain regions in individuals with comorbid depression in AD. Further work in larger cohorts is needed to understand brain region specificity of immune marker alterations and the relationship of these changes with pre-mortem clinical outcomes.
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Neuroinflammation in co-morbid depression with AD v5
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Accepted/In Press date: 23 February 2024
Additional Information:
We are very grateful to the donors and families who generously donated the samples used in this research and to the staff of the brain bank. Tissue was supplied by the South West Dementia Brain Bank which is part of the Brains for Dementia Research programme, jointly funded by Alzheimer's Research UK and Alzheimer's Society and is supported by BRACE (Bristol Research into Alzheimer's and Care of the Elderly).
We are very grateful to the Alzheimer’s Society (grant 518) who funded this research. Dr Sinclair is currently supported by the Elizabeth Blackwell Institute at the University of Bristol and the Wellcome trust institutional strategic support fund. Parts of this work contributed to an MRes for JL and an MSc in neuroscience for SS.
GMK acknowledges funding support from the Wellcome Trust (Grant No. 201486/Z/16/Z), the Medical Research Council, UK (Grant No. MC_UU_00011/1); Grant No. MR/S037675/1; and Grant No. MR/W014416/1), and the National Institute of Health Research Bristol Biomedical Research Centre, UK (Grant No. NIHR203315).
Identifiers
Local EPrints ID: 487614
URI: http://eprints.soton.ac.uk/id/eprint/487614
ISSN: 2772-4085
PURE UUID: 9c52612c-2e1d-4848-977b-3dbe426b3571
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Date deposited: 29 Feb 2024 17:36
Last modified: 18 Mar 2024 02:52
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Contributors
Author:
Jordan T. Lin
Author:
Mizuki Morisaki
Author:
Srisharnitha A. Sampathkumar
Author:
Laurie C. Lau
Author:
Golam M. Khandaker
Author:
Lindsey I. Sinclair
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