Inflammation in Dementia with Lewy bodies

Amin, Jay, Williams, Tony, Teeling, Jessica, Dorey, Robert, Williams, Daisy, Tommasino, Emmanuele, Holmes, Clive and Boche, Delphine (2017) Inflammation in Dementia with Lewy bodies. Alzheimer's & Dementia, 13 (7, Supplement), P594-P595. (doi:10.1016/j.jalz.2017.07.232).

Abstract

Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). There is mounting evidence supporting a role for inflammation in the aetiology of AD, with the innate immune cells of the brain, microglia, being key players. In contrast, our understanding of the role of inflammation in DLB is much less well developed. We hypothesise that inflammatory processes will show a profile specific to DLB and will be significantly associated with the neuropathological and clinical features of the disease. Methods: a) Neuropathology study: Post-mortem human brain sections from the middle temporal gyrus of 69 cases (38 DLB, 31 age-matched controls) were immunostained for markers of neuropathology (a-synuclein, amyloid-b, p-tau), microglial activation (Iba1, HLA-DR, CD68) and FcgRs (CD64, CD32a, CD32b and CD16). Quantification was performed to obtain protein load (%) using Image J. b) Clinical biomarker study: 90 participants (30 DLB, 30 AD, 30 controls) are entering an observational, cross-sectional study. ELISA and flow cytometry are being used to investigate blood markers of systemic inflammation. Results: a) In the DLB brain there was significantly higher a-synuclein and amyloid-b (p=0.039) protein load, with a trend for higher p-tau (p=0.052) load, compared to controls. No significant difference was found in the load of microglial activation markers Iba1 (p=0.307), HLA-DR (p=0.832) or CD68 (p=0.064). However, FcgR markers did show significantly decreased CD32a (p=0.043) and increased CD16 load (p=0.027) in DLB compared to controls, but there was no difference in CD64 (p=0.582) or CD32b load (p=0.976). No significant correlations were found between any neuropathological and any inflammatory marker in either cohort. b) Clinical study is due to complete in 2017. Conclusions: Despite the confirmation of increased neuropathology in the DLB brain, this did not appear to affect the expression of microglia, as previously seen in AD. However, the FcgR profile does appear to be modified in DLB. Ongoing work aims to investigate systemic inflammation in the clinical study, with the potential for identification of a unique inflammatory signature in DLB.

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Contributors

Author: Jay Amin

Author: Jessica Teeling

Author: Clive Holmes

Author: Delphine Boche

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