Microglial activation and dopamine terminal loss in early Parkinson's disease

Neuroinflammatory glial response may contribute to degenerative processes in Parkinson's disease (PD). To investigate changes in microglial activity associated with changes in the presynaptic dopamine transporter density in the PD brain in vivo, we studied 10 early-stage drug-naive PD patients twice using positron emission tomography with a radiotracer for activated microglia (11)C(R)-PK11195 and a dopamine transporter marker (11)CCFT. Quantitative levels of binding potentials (BPs) of (11)C(R)-PK11195 and (11)CCFT in the nigrostriatal pathway were estimated by compartment analyses. The levels of (11)C(R)-PK11195 BP in the midbrain contralateral to the clinically affected side were significantly higher in PD than that in 10 age-matched healthy subjects. The midbrain (11)C(R)-PK11195 BP levels significantly correlated inversely with (11)CCFT BP in the putamen and correlated positively with the motor severity assessed by the Unified Parkinson's Disease Rating Scale in PD. In healthy subjects, the (11)C(R)-PK11195 BP in the thalamus and midbrain showed an age-dependent increase. In vivo demonstration of parallel changes in microglial activation and corresponding dopaminergic terminal loss in the affected nigrostriatal pathway in early PD supports that neuroinflammatory responses by intrinsic microglia contribute significantly to the progressive degeneration process of the disease and suggests the importance of early therapeutic intervention with neuroprotective drugs.