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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

Chong, J. R.; Hilal, S.; Venketasubramanian, N.; Scholl, M.; Blennow, K.; Ashton, N. J.; Zetterberg, H.; Chen, C. P.; Lai, M. K. P.

2025-12-11 neurology
10.64898/2025.12.09.25341888 medRxiv
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INTRODUCTIONWe evaluated the performance of plasma brain-derived (BD)- as well as total-p-Tau181, p-Tau217 and p-Tau231 in detecting beta-amyloid positivity (A{beta}+) and cognitive decline in a Singapore-based cohort of older people with cerebrovascular disease. METHODSBrain amyloid status (A{beta}- [n = 139] vs A{beta}+ [n = 74]) was determined by positron emission tomography (PET) scans. Plasma BD and total p-Tau were measured using NUcleic acid Linked Immuno-Sandwich Assay multiplexing platform (NULISAseq). RESULTSBD-p-Tau217 (area under the curve [AUC] = 0.965) outperformed other BD and total-p-Tau species in detecting PET A{beta}+ (AUC = 0.823-0.937; all p [≤] 0.008). Using three-range or binary references, BD-p-Tau217 demonstrated high sensitivity (>90%), specificity (>90%), positive (>85%) and negative (>95%) predictive values. BD-p-Tau217-derived High-risk group exhibited faster cognitive decline than the Low-risk group. DISCUSSIONRisk stratification for PET A{beta}+ based on plasma BD-p-Tau217 suggests superior diagnostic and prognostic utility, warranting further assessment.

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