Plasma brain-derived p-Tau217 outperforms other p-Tau species in detecting abnormal brain amyloid in an Asian cohort of older people with cerebrovascular disease burden.

BACKGROUND

Plasma brain derived-p-Tau217 (BD-p-Tau217) may outperform total-p-Tau217 in detecting brain amyloid burden and warrants evaluation.

OBJECTIVES

To perform head-to-head comparison of plasma BD- as well as total-p-Tau181, p-Tau217 and p-Tau231 for detecting beta-amyloid positivity (Aβ+), evaluate reference ranges for Aβ+, and assess the prognostic utility of BD-p-Tau217 reference ranges.

DESIGN

Observational study.

SETTING

Participants recruited from memory clinics and the community in Singapore.

PARTICIPANTS

213 participants, including 44 cognitively normal, 107 cognitively impaired no dementia, and 62 dementia (mean [SD] age, 73 [1] years; 121 females).

MEASUREMENTS: Amyloid status (Aβ- [n = 139] vs Aβ+ [n = 74]) was determined by positron emission tomography (PET). Plasma BD-p-Tau and total-p-Tau were measured using the NULISAseq™ CNS Disease Panel 120. The diagnostic performance for detecting Aβ+, reference ranges (three-range: 95% specificity/95% sensitivity); binary: maximizing Youden index), and the prognostic performance of p-Tau biomarkers were evaluated.

RESULTS

Plasma BD-p-Tau217 (AUC = 0.965) outperformed other BD- and total-p-Tau species in detecting PET Aβ+ (AUC = 0.823-0.937; all p ≤ 0.008). Using a three-range reference, BD-p-Tau217 achieved positive predictive value (PPV) and negative predictive value (NPV) of 90% and 97%, respectively. Proportion of participants in the intermediate-risk group was 7% (n = 14). Applying a binary reference, BD-p-Tau217 achieved both a specificity and sensitivity of 92%, with PPV and NPV of 86% and 96%, respectively. BD-p-Tau217-derived high-risk group exhibited faster cognitive decline than the low-risk group.

CONCLUSIONS

Risk stratification for PET Aβ+ based on plasma BD-p-Tau217 suggests superior diagnostic and prognostic utility, warranting further validation.