Background:
Several TSPO PET studies have shown increased glial cell density inParkinson’s disease (PD). However, TSPO PET cannot discriminate between pro- andanti-inflammatory microglia, thereby limiting the understanding of pro-inflammatorycontributions to PD pathogenesis. Therefore, this study focused on the novelradiotracer [11 C]SMW139 targeting the P2X7 receptor (P2X7R), which is specificallyexpressed on pro-inflammatory microglia. We aim to investigate pro-inflammatorysignals in PD using [11C]SMW139 PET.

Method:
15 PD patients (age: 67, 67% male) and 15 controls (HC) (age: 64,47% male) were included from Amsterdam UMC, Turku University Hospital andKarolinska Institutet. All participants underwent a 90 min [11 C]SMW139 PET scanwith arterial sampling, resulting in the outcome measure VTp (Volume of distribution).[ 11 C]SMW139 VTp was quantified in several regions of interest (ROIs)(Figure 1).Differences in [11 C]SMW139 VTp between PD and HC were assessed using linearmixed models with post hoc testing. Associations between motor symptom severity asmeasured by UPDRS-III, disease duration and [11 C]SMW139 VTp were assessed usinglinear regressions.

Result:
In the a-priori ROIs, PD patients showed significantly higher VTp in the putamen(β=0.04, p =0.046) and whole cortex (β= 0.04, p =0.043) compared to HC, indicatinghigher pro-inflammatory activity (Figure 1). In an exploratory analysis, PD patients also showed higher VTp in the orbitofrontal cortex (β= 0.04, p =0.041). There wasno significant association between VTp and symptom severity (brainstem: β=-0.002,p =0.084; caudate nucleus; β= -0.002, p = 0.164800; putamen: β= -0.002, p =0.265,whole cortex: β= -0.002, p =0.119) or disease duration in PD (brainstem: β= -0.01, p=0.055; caudate nucleus; β= -0.005, p = 0.282; putamen: β= -0.01, p =0.113, wholecortex: β= -0.007, p =0.217) (Figure 2). However, there was a negative trend indicatinghigher pro-inflammatory activation earlier in the disease trajectory, which warrantsfurther investigation (Figure 2 & 3).

Conclusion:
​​​​​​​PD patients showed increased P2X7R binding in the putamen and braincortex, as assessed by [ 11 C]SMW139 PET, suggesting the presence of increased levelsof pro-inflammatory microglia.