Objective: To evaluate the relationship between microglial activation and amyloid-β deposition in the brain using positron emission tomography (PET) in Parkinson’s disease (PD) with normal and impaired cognitive function.

Background: Neuroinflammatory processes such as activated microglia have been reported to play an important role in PD. Deterioration of cognitive performance has been connected with elevated beta-amyloid accumulation. Accumulation of amyloid- β may contribute to microglial activation and disease progression.

Methods: We recruited 17 PD patients, 11 PD patients with mild cognitive impairment (MCI) and 11 healthy controls (HCs) to measure the impact of amyloid-β deposition in the brain with [¹¹C] Pittsburgh compound B (PIB) on microglial activation using the translocator protein 18-kDa (TSPO) radioligand [¹⁸F]-FEPPA. PIB distribution volume ratio (DVR) was measured in cortical and subcortical regions. A DVR of 1.2 was set to divide each brain region into PIB-positive or PIB-negative. FEPPA total distribution volume (V_T) values were compared for each brain region to evaluate the effect of PIB positivity while adjusting for TSPO rs6971 polymorphism (which is implicated in differential binding affinity).

Results: Preliminary analyzes revealed a significant main effect of PIB positivity in the striatum (F_{(2, 32)}= 5.9, p = 0.006). Besides the striatum (p=.019), the dorsolateral (p=.012) and prefrontal cortex (p=.002) as well as the temporal (p=.004) and frontal lobe (p=.006) showed a significant interaction effect. In these regions the effect of PIB positivity was only significant in the PD-MCI group. In the frontal lobe the effect of PIB positivity was also significant in the PD group (p=.011). Further, PIB-positive PD-MCI patients showed significantly higher V_T values than PIB-positive HCs in the striatum (p=.019), temporal (p=.012) and frontal lobe (p=.031) as well as significantly higher V_T values than PIB-positive PDs in the striatum (p=.028), prefrontal cortex (p=.004) and temporal lobe (p=.011).

Conclusions: Our results indicate an interaction between amyloid-β deposition and microglial activation in PD. Further investigations are necessary to evaluate if amyloid deposits cause neuroinflammation and further neurodegeneration or if increased microglia activation develops as a protective response.

References: Partially presented at the 1st Pan American PD and MDS Congress in Miami, Florida, USA, February 24-26, 2017;    McGeer, Itagaki et al. 1988, Petrou, Bohnen et al. 2012

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MDS Abstracts - https://www.mdsabstracts.org/abstract/interactions-between-amyloid-%ce%b2-and-microglial-activation-in-parkinsons-disease/