Multimodal neuroimaging elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in Parkinson's disease.

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Parkinson's disease (PD) exhibits a characteristic posterior-to-anterior gradient of striatal dopamine loss, yet the underlying upstream mechanisms remain unclear. We combined in vivo ¹⁸F-FPCIT dopamine transporter (DaT) PET/MRI, quantitative susceptibility mapping, and diffusion MRI tractography in 48 PD patients and 10 healthy controls to test whether substantia nigra pars compacta (SNc) iron and microstructural disruption mediate posterior putaminal vulnerability. PD patients showed marked posterior putamen (pPut) DaT reduction (~60%) and elevated SNc iron. SNc iron negatively correlated with striatal DaT availability, and nigrostriatal pathways to the pPut exhibited higher axial diffusivity. Serial mediation analyses demonstrated that SNc iron indirectly impaired striatal DaT function via reduced SNc DaT binding. Putaminal DaT-SBR robustly discriminated PD from controls (AUC 0.93-0.96), exceeding caudate performance. Transgenic and α-synuclein preformed fibril mouse models provided qualitative anatomical support. These findings identify SNc iron-related degeneration as a key driver of posterior striatal vulnerability in PD.

Related topics