npj Parkinson's Disease (Aug 2023)

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

  • Wataru Uchida,
  • Koji Kamagata,
  • Christina Andica,
  • Kaito Takabayashi,
  • Yuya Saito,
  • Mana Owaki,
  • Shohei Fujita,
  • Akifumi Hagiwara,
  • Akihiko Wada,
  • Toshiaki Akashi,
  • Katsuhiro Sano,
  • Masaaki Hori,
  • Shigeki Aoki

DOI
https://doi.org/10.1038/s41531-023-00565-2
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 11

Abstract

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Abstract 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.