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Peer-reviewedCC BY-NC-ND 4.0European Journal of Nuclear Medicine and Molecular Imaging

Selective white matter tract vulnerability associated with tau burden in progressive supranuclear palsy and Alzheimer’s disease

  • Chi-Wei Huang1
  • Hsin-I Chang1
  • Ting-Yu Chang2
  • Kun-Ju Lin3
  • Shih-Wei Hsu4
  • Chen-Chang Lee4
  • Shu-Hua Huang5
  • Chiung-Chih Chang1,6
6 affiliations
  1. 1Department of Neurology, Cognition and Aging Center, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123 Ta-Pei Rd., Niau-Sung Dist, Kaohsiung City, 833401 Taiwan
  2. 2Department of Neurology, Stroke Center, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, No 5. Fuxing St., Guishan District, Taoyuan, Taiwan
  3. 3Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, No 5. Fuxing St., Guishan District, Taoyuan, 33305 Taiwan
  4. 4Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  5. 5Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123 Ta-Pei Rd., Niau-Sung Dist, Kaohsiung City, 833401 Taiwan
  6. 6School of Medicine, College of Medicine, National Sun Yat-sen University, No 70, Lienhai Road, Kaohsiung, 80424 Taiwan
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Abstract

Purpose: Progressive supranuclear palsy (PSP) and Alzheimer’s disease (AD) exhibit different tau distributions. We compared tract-specific associations between florzolotau(18F) retention, white matter (WM) microstructure, and clinical impairment.

Methods: Forty-nine patients with PSP, 40 with AD, and 30 cognitively unimpaired controls underwent florzolotau(18F) PET. Tractography evaluated projection and association fibers, including the dentatorubrothalamic tract (DRTT) and superior longitudinal fasciculus (SLF). Regional SUVRs were calculated using WM-PERSI normalization. Associations among uptake, diffusion measures, brain volume, and clinical outcomes were evaluated using covariate-adjusted correlations with Bonferroni correction, partial canonical correlation, and exploratory path analyses.

Results: PSP was characterized by predominantly subcortical and brainstem florzolotau(18F) retention and more extensive WM abnormalities, including DRTT involvement. AD showed predominantly cortical retention and microstructural abnormalities of SLF branches. In PSP, regional subcortical uptake was associated with DRTT microstructure, while DRTT mean diffusivity and frontal volume contributed most strongly to the canonical variate associated with motor impairment (canonical correlation = 0.82, p = 0.001). In AD, cortical uptake was associated with SLF microstructure, while cortical volume and SLF mean diffusivity contributed to the canonical variate associated with executive function (canonical correlation = 0.83, p = 0.001). Exploratory path models were consistent with indirect associations involving white matter microstructure and cortical volume.

Conclusion: PSP and AD showed distinct patterns of tract vulnerability associated with regional florzolotau(18F) retention and clinical impairment. These cross-sectional findings support further longitudinal investigation of disease-specific network degeneration.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08121-9.

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Cite

BibTeXRIS
BibTeX
@article{huang2026selective,
  title = {{Selective white matter tract vulnerability associated with tau burden in progressive supranuclear palsy and Alzheimer’s disease}},
  author = {Chi-Wei Huang and Hsin-I Chang and Ting-Yu Chang and Kun-Ju Lin and Shih-Wei Hsu and Chen-Chang Lee and Shu-Hua Huang and Chiung-Chih Chang},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = aug,
  doi = {10.1007/s00259-026-08121-9},
  url = {https://doi.org/10.1007/s00259-026-08121-9},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Selective white matter tract vulnerability associated with tau burden in progressive supranuclear palsy and Alzheimer’s disease
AU  - Chi-Wei Huang
AU  - Hsin-I Chang
AU  - Ting-Yu Chang
AU  - Kun-Ju Lin
AU  - Shih-Wei Hsu
AU  - Chen-Chang Lee
AU  - Shu-Hua Huang
AU  - Chiung-Chih Chang
PY  - 2026
DA  - 2026/08/12
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08121-9
UR  - https://doi.org/10.1007/s00259-026-08121-9
AB  - Purpose: Progressive supranuclear palsy (PSP) and Alzheimer’s disease (AD) exhibit different tau distributions. We compared tract-specific associations between florzolotau(18F) retention, white matter (WM) microstructure, and clinical impairment.  Methods: Forty-nine patients with PSP, 40 with AD, and 30 cognitively unimpaired controls underwent florzolotau(18F) PET. Tractography evaluated projection and association fibers, including the dentatorubrothalamic tract (DRTT) and superior longitudinal fasciculus (SLF). Regional SUVRs were calculated using WM-PERSI normalization. Associations among uptake, diffusion measures, brain volume, and clinical outcomes were evaluated using covariate-adjusted correlations with Bonferroni correction, partial canonical correlation, and exploratory path analyses.  Results: PSP was characterized by predominantly subcortical and brainstem florzolotau(18F) retention and more extensive WM abnormalities, including DRTT involvement. AD showed predominantly cortical retention and microstructural abnormalities of SLF branches. In PSP, regional subcortical uptake was associated with DRTT microstructure, while DRTT mean diffusivity and frontal volume contributed most strongly to the canonical variate associated with motor impairment (canonical correlation = 0.82, p = 0.001). In AD, cortical uptake was associated with SLF microstructure, while cortical volume and SLF mean diffusivity contributed to the canonical variate associated with executive function (canonical correlation = 0.83, p = 0.001). Exploratory path models were consistent with indirect associations involving white matter microstructure and cortical volume.  Conclusion: PSP and AD showed distinct patterns of tract vulnerability associated with regional florzolotau(18F) retention and clinical impairment. These cross-sectional findings support further longitudinal investigation of disease-specific network degeneration.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08121-9.
SN  - 1619-7070
SN  - 1619-7089
ER  -