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Peer-reviewedCC BY-NC-ND 4.0NPJ Parkinson's Disease

Plasma pTau217 and pTau231 predict progression to dementia in Parkinson’s disease: a prospective longitudinal study

  • Cheng-Hsuan Li1,2,3
  • Ting-Wen Cheng1
  • Chin-Hsien Lin1,3,4,5,6
6 affiliations
  1. 1Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
  2. 2Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
  3. 3Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  4. 4Department of Biomedical Engineering, College of Medical Science and Technology, National Taiwan University, Taipei, Taiwan
  5. 5Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  6. 6Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan
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Abstract

This prospective study evaluated the prognostic utility of Alzheimer’s disease-related plasma biomarkers (phosphorylated tau [pTau217 and pTau231], the amyloid-β [Aβ] 42/40 ratio) and neurofilament light chain (NfL) in 123 Parkinson’s disease (PD) patients and 40 controls. Over a mean 5.1-year follow-up, 35 of 109 initially non-demented PD patients (32.1%) progressed to dementia. Plasma pTau217 and NfL levels were elevated, whereas the Aβ42/40 ratio was reduced, in cognitively impaired PD groups versus controls. Baseline pTau217 accurately differentiated dementia converters from non-converters (AUC = 0.877; 95% CI: 0.798–0.956). Patients with pTau217 ≥ 0.268 pg/mL had a higher risk of dementia progression (HR: 5.49; 95% CI: 2.37–12.74). This risk was further elevated in patients in the highest quartile ( ≥ 0.36 pg/mL; HR: 11.35; 95% CI: 2.60–49.59) versus the lowest quartile ( < 0.20 pg/mL). Similarly, the pTau231 cut-off ( ≥ 2.575 pg/mL) predicted an increased risk of dementia (HR: 3.89; 95% CI: 1.67–9.03). Both pTau217 and pTau231 demonstrated high predictive performance in Cox models (C-index: 0.806 and 0.796, respectively). Plasma NfL exhibited longitudinal increases during follow-up. Baseline plasma pTau217 and pTau231 serve as surrogate markers for predicting dementia progression in PD. Further validation of these biomarker cut-off values is warranted.

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Cite

BibTeXRIS
BibTeX
@article{li2026plasma,
  title = {{Plasma pTau217 and pTau231 predict progression to dementia in Parkinson’s disease: a prospective longitudinal study}},
  author = {Cheng-Hsuan Li and Ting-Wen Cheng and Chin-Hsien Lin},
  journal = {NPJ Parkinson's Disease},
  year = {2026},
  month = jul,
  doi = {10.1038/s41531-026-01469-7},
  url = {https://doi.org/10.1038/s41531-026-01469-7},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Plasma pTau217 and pTau231 predict progression to dementia in Parkinson’s disease: a prospective longitudinal study
AU  - Cheng-Hsuan Li
AU  - Ting-Wen Cheng
AU  - Chin-Hsien Lin
PY  - 2026
DA  - 2026/07/11
JO  - NPJ Parkinson's Disease
DO  - 10.1038/s41531-026-01469-7
UR  - https://doi.org/10.1038/s41531-026-01469-7
AB  - This prospective study evaluated the prognostic utility of Alzheimer’s disease-related plasma biomarkers (phosphorylated tau [pTau217 and pTau231], the amyloid-β [Aβ] 42/40 ratio) and neurofilament light chain (NfL) in 123 Parkinson’s disease (PD) patients and 40 controls. Over a mean 5.1-year follow-up, 35 of 109 initially non-demented PD patients (32.1%) progressed to dementia. Plasma pTau217 and NfL levels were elevated, whereas the Aβ42/40 ratio was reduced, in cognitively impaired PD groups versus controls. Baseline pTau217 accurately differentiated dementia converters from non-converters (AUC = 0.877; 95% CI: 0.798–0.956). Patients with pTau217 ≥ 0.268 pg/mL had a higher risk of dementia progression (HR: 5.49; 95% CI: 2.37–12.74). This risk was further elevated in patients in the highest quartile ( ≥ 0.36 pg/mL; HR: 11.35; 95% CI: 2.60–49.59) versus the lowest quartile ( < 0.20 pg/mL). Similarly, the pTau231 cut-off ( ≥ 2.575 pg/mL) predicted an increased risk of dementia (HR: 3.89; 95% CI: 1.67–9.03). Both pTau217 and pTau231 demonstrated high predictive performance in Cox models (C-index: 0.806 and 0.796, respectively). Plasma NfL exhibited longitudinal increases during follow-up. Baseline plasma pTau217 and pTau231 serve as surrogate markers for predicting dementia progression in PD. Further validation of these biomarker cut-off values is warranted.
SN  - 2373-8057
ER  -