Ano de Publicação: 2020
AUTORIA
Jay Amin 1,2, Clive Holmes1,2, Robert B. Dorey1, Emanuele Tommasino 1, Yuri R. Casal 1, Daisy M. Williams1, Charles Dupuy1, James A. R. Nicoll1,3 and Delphine Boche 1
RESUMO
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.