Objective: To evaluate, at post-mortem, the pattern and characteristics of neuroinflammatory change in Parkinson’s disease (PD) brain and to assess its relationship with aberrant alpha-synuclein, tau and rate of cognitive decline during life.

Background: Post-mortem and in vivo PET neuroimaging studies have demonstrated evidence of inflammation in the PD brain, but its relationship with cortical Lewy body pathology, Alzheimer’s type pathology, and the development of dementia in PD is unknown.

Methods: Neuropathological examination of paraffin-embedded sections (hippocampus, entorhinal, and temporal cortex) from 18 PD and 9 control brains (without neurological disease) was performed following immunohistochemical staining for α-synuclein, tau and neuroinflammatory markers (HLA-DR, Iba-1, GFAP). Lewy body counts and neurofibrillary tangles (NFTs) were evaluated semi-quantitatively. Activated microglia and hypertrophied astrocytes were quantified using automated image analysis software (Image-J). Relationships between pathological markers, dementia status and rate of cognitive decline (MMSE change/year) were evaluated.

Results: PD and control brains were age matched (mean(SD) 80.42(6.92) and 80.11(5.21) respectively). Lewy body counts were higher in PD cases than controls in all regions examined, as expected (p<0.001), and activated microglia counts were higher in the hippocampus in PD versus controls (p=0.05) There were no case-control differences in NFTs and astrocytic activation. Comparing PD dementia versus PD non-dementia cases, Lewy body counts, NFTs and hypertrophied astrocytes did not differ significantly. However, there was a trend towards higher activated microglia counts in PD dementia versus non dementia cases and controls in the temporal cortex, and activated microglia counts in this brain region correlated with rate of cognitive decline in PD (Pearson’s r=0.713, p=0.009). No other pathological markers correlated significantly with cognitive decline, and no correlations were observed between Lewy body counts or NFTs and neuroinflammatory markers.

Conclusions: Microglial activation in temporal regions is a better pathological correlate of cognitive decline in PD than Lewy body pathology or NFTs, and may develop as a leading front catalysing the development of dementia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-neuroinflammation-in-the-development-of-parkinsons-disease-dementia/