Decreased neuronal and increased endothelial fractalkine expression are associated with neuroinflammation in Parkinson's disease and related disorders.

Introduction: Chronic neuroinflammation is a persistent feature of individuals with Parkinson's disease (PD). Dopaminergic neurodegeneration is partially associated with neuroinflammation. Neuron-to-microglia communication via fractalkine (CX3CL1) and its receptor plays a significant role in neuroinflammation. The relationship between fractalkine signaling and neuroinflammatory activities has been studied in animal models of PD, but its role is unclear in human PD. The current study aimed to elucidate the neuron-microglia communication between neuronal and endothelial fractalkine ligand expression, microglial activity, and CD4 Methods: Brain sections were obtained from age-matched control subjects with no motor deficits (control, Results: In PD, MMD-LB, and PSP postmortem brains, fractalkine expression in remaining nigral neurons was significantly reduced but markedly increased in blood vessel endothelial cells. The density of microglia and CD4 Discussion: The downregulation of neuronal fractalkine expression caused by protein inclusions, such as abnormal alpha-synuclein or tau, is linked to microglia activation. When activated, microglia release cytokines that further stimulate endothelial cells to express fractalkine. This process recruits peripheral T cells, which infiltrate the injured brain. These findings indicate that the varying levels of neuronal and endothelial fractalkine expression in the substantia nigra contribute to neuroinflammatory activity in both synucleinopathy and tauopathy.