Fiber-specific micro- and macroscopic white matter alterations in progressive supranuclear palsy and corticobasal syndrome

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are characterized by progressive white matter (WM) alterations associated with the prion-like spreading of four-repeat tau, which has been pathologically confirmed. It has been challenging to monitor the WM degeneration patterns underlying the clinical deficits in vivo. Here, a fiber-specific fiber density and fiber cross-section, and their combined measure estimated using fixel-based analysis (FBA), were cross-sectionally and longitudinally assessed in PSP (n = 20), CBS (n = 17), and healthy controls (n = 20). FBA indicated disease-specific progression patterns of fiber density loss and subsequent bundle atrophy consistent with the tau propagation patterns previously suggested in a histopathological study. This consistency suggests the new insight that FBA can monitor the progressive tau-related WM changes in vivo. Furthermore, fixel-wise metrics indicated strong correlations with motor and cognitive dysfunction and the classifiability of highly overlapping diseases. Our findings might also provide a tool to monitor clinical decline and classify both diseases.

Automated summary

This study used fixel-based analysis to evaluate white matter damage in patients with progressive supranuclear palsy and corticobasal syndrome. It found that fiber density and fiber cross-section loss patterns were associated with clinical symptoms, consistent with previous histopathological studies on tau protein propagation. The study suggests that fixel-based analysis can monitor tau-related white matter changes in real-time.