Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the appearance of α-
synuclein insoluble aggregates known as Lewy bodies. Neurodegeneration is accompanied by
neuroinflammation mediated by
cytokines and
chemokines produced by the activated microglia. Several studies demonstrated that such an inflammatory process is an early event, and contributes to oxidative stress and
mitochondrial dysfunctions. α-
synuclein fibrillization and aggregation activate microglia and contribute to disease onset and progression. Mutations in different genes exacerbate the inflammatory phenotype in the monogenic compared to sporadic forms of PD. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) with selected
radiopharmaceuticals allow in vivo imaging of molecular modifications in the brain of living subjects. Several publications showed a reduction of dopaminergic terminals and
dopamine (DA) content in the basal ganglia, starting from the early stages of the disease. Moreover, non-dopaminergic neuronal pathways are also affected, as shown by in vivo studies with serotonergic and glutamatergic radiotracers. The role played by the immune system during illness progression could be investigated with PET
ligands that target the microglia/macrophage Translocator
protein (TSPO) receptor. These agents have been used in PD patients and rodent models, although often without attempting correlations with other molecular or functional parameters. For example, neurodegeneration and brain plasticity can be monitored using the metabolic marker 2-Deoxy-2-[18F]fluoroglucose ([18F]-FDG), while oxidative stress can be probed using the
copper-labeled
diacetyl-bis(N-methyl-
thiosemicarbazone) ([
Cu]-ATSM) radioligand, whose striatal-specific binding ratio in PD patients seems to correlate with a disease rating scale and motor scores. Also, structural and functional modifications during
disease progression may be evaluated by Magnetic Resonance Imaging (MRI), using different parameters as
iron content or cerebral volume. In this review article, we propose an overview of in vivo clinical and non-clinical imaging research on
neuroinflammation as an emerging marker of early PD. We also discuss how multimodal-imaging approaches could provide more insights into the role of the inflammatory process and related events in PD development.