Neuroinflammation in dementia with Lewy bodies: a human post-mortem study
Autor: | Daisy M Williams, James A. R. Nicoll, Jay Amin, Yuri R Casal, Delphine Boche, Clive Holmes, Robert B Dorey, Charles Dupuy, Emanuele Tommasino |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Lewy Body Disease Pathology medicine.medical_specialty Physiology Neuropathology Molecular neuroscience behavioral disciplines and activities Article lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Alzheimer Disease mental disorders medicine Neuropil Dementia Humans lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Neuroinflammation Inflammation Dementia with Lewy bodies business.industry Neurodegeneration medicine.disease nervous system diseases Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure nervous system Cerebral cortex Autopsy Microglia business 030217 neurology & neurosurgery Spongiosis |
Zdroj: | Translational Psychiatry, Vol 10, Iss 1, Pp 1-11 (2020) Translational Psychiatry |
ISSN: | 2158-3188 |
Popis: | Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer’s disease (AD). It is now established that cerebral inflammation has a key role in the aetiology and progression of AD, but this has yet to be confirmed in DLB. We aimed to determine the neuroinflammatory profile in the cerebral cortex of a large cohort of DLB cases. Thirty post-mortem confirmed DLB cases and twenty-nine matched controls were immunolabelled (Brodmann area 21) and quantified for: neuropathology—αSYN, Aβ, P-tau; microglial phenotype—Iba1, HLA-DR, CD68, FcƴR (CD64, CD32a, CD32b, CD16); presence of T lymphocytes—CD3; and anti-inflammatory markers—IL4R, CHI3L1. Status spongiosis, as a marker of neuropil degeneration, was quantified using Haematoxylin and Eosin staining. We found no significant difference between groups in protein load for Iba1, HLA-DR, CD68, CD64, CD32b, IL4R, or CHI3L1, despite increased neuropathology in DLB. CD32a load was significantly lower, and CD16 load higher, in DLB compared with controls. There was no difference in status spongiosis between groups. Significantly more DLB cases than controls showed T-lymphocyte recruitment. Overall, we conclude that microglial activation is not a prominent feature of DLB, and that this may be associated with the relatively modest neuropil degeneration observed in DLB. Our findings, based on the largest post-mortem cohort to date exploring neuroinflammation in DLB, demonstrate a dissociation between protein deposition, neurodegeneration and microglial activation. The relative preservation of cortical structures in DLB suggests the dementia could be more amenable to potential therapies. |
Databáze: | OpenAIRE |
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