Fig. 4. Diffusion tractography reveals subregional vulnerability of the nigrostriatal pathway in PD and supporting evidence from the α-synuclein PFF mouse model.
A Representative DTI tractography of bilateral SNc-striatal pathways in a HC and a patient with PD, including SNc-caudate, SNc-putamen, SNc-aPut, and SNc-pPut. Fiber colors indicate the principal diffusion direction (red: left–right; green: anterior–posterior; blue: superior–inferior). B Group comparisons of diffusion metrics in PD patients, showing pronounced alterations in SNc-Put pathways compared with SNc-Cd, and greater vulnerability of the SNc-pPut pathway relative to the SNc-aPut pathway. All data in (B) represent PD patients (n = 48). C Staining of TH (yellow) and α-synuclein (green) in α-synuclein SNc-injected PFF mouse brain. pS129 signals were restricted to the ipsilateral medial striatum, 12 weeks after the unilateral injection of α-synuclein PFF into the SNc of the mouse brain. AD axial diffusivity, aPut anterior putamen, Cd caudate, FA fractional anisotropy, Nuclei counterstained with DAPI (blue). Scale bar = 1 mm (row 1) and 800 μm (row 2). AD axial diffusivity, aPut anterior putamen, Cd caudate, FA fractional anisotropy, DAPI 4’, 6-diamidino-2-phenylindole, DTI diffusion tensor imaging, MD mean diffusivity, PFF preformed fibril, PD Parkinson’s disease, pPut posterior putamen, pS129 phospho-α-synuclein, Put putamen, RD radial diffusivity, SNc substantia nigra pars compacta, TH tyrosine hydroxylase, ns not significant; ***p < 0.001; ****p < 0.0001.