Biomarkers Significance 6/10

Plasma pTau217 and pTau231 predict dementia progression in Parkinson’s disease

Investigators prospectively evaluated plasma Alzheimer’s disease biomarkers in 123 Parkinson’s disease patients and 40 controls over a mean 5.1-year follow-up. Baseline pTau217 and pTau231 levels accurately distinguished patients who progressed to dementia from those who remained cognitively stable, with pTau217 achieving an AUC of 0.877 and hazard ratios up to 11.35 for the highest concentration quartile. Plasma neurofilament light chain showed longitudinal increases during follow-up. These findings position plasma pTau217 and pTau231 as promising surrogate markers for neurodegenerative risk stratification in Parkinson’s disease, though independent validation of proposed cut-off values is required before clinical implementation.

The original study

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

Authors
Li CH, Cheng TW, Lin CH
Journal
NPJ Parkinson's disease
Type
Journal Article
PMID
42436138
Read the original study →

Original 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.