Optimizing Lumipulse plasma pTau217/Aβ42 ratio cutpoints in an Asian cohort with high cerebrovascular disease burden
- 1Yong Loo Lin School of Medicine, National University of Singapore
Abstract
The generalizability of FDA-cleared Lumipulse plasma pTau217 / A{beta}42 ratio cutpoints to Asian populations remains uncertain, especially in those with high burden of concomitant cerebrovascular disease (CeVD). We evaluated pTau217, A{beta}42 and their ratio in 205 Singapore-based participants with corresponding amyloid neuroimaging. In-house cutpoints were derived using a three-range strategy targeting 95% sensitivity and specificity. Plasma pTau217/A{beta}42 ratio outperformed pTau217 alone (area under the curve, 0.951 versus 0.925; p=0.004), with comparable performance across CeVD severities. Plasma ratio cutpoints achieved 98% negative predictive value, 88% positive predictive value, and 95% accuracy, classifying 10% as intermediate-risk. Using FDA-cleared cutpoints for our cohort retained 97% sensitivity and negative predictive value but yielded lower specificity (86%), positive predictive value (77%) and accuracy (85%), with 29% classified as intermediate-risk. Our findings support the need for population-specific validation of cutpoints from FDA-cleared blood biomarkers of brain amyloid pathology.
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BibTeX
@misc{chong2026optimizing,
title = {{Optimizing Lumipulse plasma pTau217/Aβ42 ratio cutpoints in an Asian cohort with high cerebrovascular disease burden}},
author = {J. R. Chong and A. T. Y. Yam and A. Toh and G. Jiang and T. Ito and C. Kobayashi and A. Dash and P. Sachdev and C. P. Chen and M. K. Lai},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.26367313},
url = {https://www.medrxiv.org/content/10.64898/2026.11.04.26367313v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Optimizing Lumipulse plasma pTau217/Aβ42 ratio cutpoints in an Asian cohort with high cerebrovascular disease burden
AU - J. R. Chong
AU - A. T. Y. Yam
AU - A. Toh
AU - G. Jiang
AU - T. Ito
AU - C. Kobayashi
AU - A. Dash
AU - P. Sachdev
AU - C. P. Chen
AU - M. K. Lai
PY - 2026
DA - 2026/11/04
PB - medRxiv
DO - 10.64898/2026.11.04.26367313
UR - https://www.medrxiv.org/content/10.64898/2026.11.04.26367313v1
AB - The generalizability of FDA-cleared Lumipulse plasma pTau217 / A{beta}42 ratio cutpoints to Asian populations remains uncertain, especially in those with high burden of concomitant cerebrovascular disease (CeVD). We evaluated pTau217, A{beta}42 and their ratio in 205 Singapore-based participants with corresponding amyloid neuroimaging. In-house cutpoints were derived using a three-range strategy targeting 95% sensitivity and specificity. Plasma pTau217/A{beta}42 ratio outperformed pTau217 alone (area under the curve, 0.951 versus 0.925; p=0.004), with comparable performance across CeVD severities. Plasma ratio cutpoints achieved 98% negative predictive value, 88% positive predictive value, and 95% accuracy, classifying 10% as intermediate-risk. Using FDA-cleared cutpoints for our cohort retained 97% sensitivity and negative predictive value but yielded lower specificity (86%), positive predictive value (77%) and accuracy (85%), with 29% classified as intermediate-risk. Our findings support the need for population-specific validation of cutpoints from FDA-cleared blood biomarkers of brain amyloid pathology.
ER -