Neuroinflammation in dementia with Lewy bodies: a human post-mortem study

Abstract

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 antiinflammatory 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.

Neuroinflammation and protein pathology in Parkinson’s disease dementia

“…Control n = 12, PDND n = 16, PDD n = 10. Quantification of parenchymal CD4 + (p = 0.081) and CD8 + T lymphocytes (p = 0.434) per mm 2 Notably, we did not observe any significant differences in tau pathology between PDND and PDD cases. In agreement, semi-quantitative scoring in a large postmortem study revealed similar levels or neurofibrillary tau tangles in the temporal, mid-frontal, and parietal cortex of PDND and PDD cases [38].…”

“…A second recent study in DLB cases showed increased T lymphocyte infiltration in both the grey and white matter of the middle temporal gyrus, in the absence of prominent microglial activation [2]. Similarly, in the substantia nigra of cases with multiple system atrophy compared to controls both CD4 + and CD8 + T lymphocytes were found to be increased [75].…”

“…The appropriate brightness threshold was manually determined to create an overlay mask. The particle analysis plugin was used to count the number of activated microglia per mm 2 . Size settings were optimized to primarily include enlarged amoeboid (activated microglia) and not small, ramified cells.…”

Parkinson disease-associated cognitive impairment

“…3) 84 . Of note, neuroinflammation is not a substantive feature of individuals with Lewy pathologies in the absence of AD pathologies 85 . The most common neuropathology in PDD is limbic and/or neocortical Lewy pathology, with few documented cases without this pathology 86 .…”

Alterações Neuropsicológicas Na Demência Por Corpos De Lewy

“…A demência por corpos de Lewy (DCL) consiste em uma patologia associada a depósitos cerebrais anormais da proteína alfa-sinucleína, os quais formam os corpos de Lewy, sendo considerada na atualidade a segunda causa neurodegenerativa mais comum de demência, somente atrás da Doença de Alzheimer (AMIN et al, 2020;MCKEITH, 2007;MCKEITH et al, 1996).…”