Quantitative Relationship Between Lumipulse G Measures of pTau217 in Plasma and the Temporal Cortex.
10 affiliations
- 1Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Belgium.
- 2Laboratory for Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Belgium.
- 3Laboratory of Neuropathology, Department of Imaging and Pathology and Leuven Brain Institute, KU Leuven, Belgium.
- 4Biomarker Development, Fujirebio Europe nv, Ghent, Belgium.
- 5VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
- 6Department of Biomedical Sciences, University of Antwerp, Belgium.
- 7Department of Neurology, University of Ulm, Germany.
- 8Department of Pathology, University Hospitals Leuven, Belgium.
- 9Laboratory Medicine Department, University Hospitals Leuven, Belgium; and.
- 10Neurology Department, University Hospitals Leuven, Belgium.
Abstract
Background and objectives
Phosphorylated tau217 (pTau217) plasma assays have shown high diagnostic accuracy for Alzheimer disease (AD). However, validation of plasma pTau217 as a direct marker of brain-based pTau pathology requires understanding of its quantitative relationship with cortical pTau217. The primary objective of this postmortem validation study was to determine the quantitative relationship of plasma pTau217 levels and the pTau217/β-amyloid (Aβ)₁₋₄₂ ratio with cortical pTau217 levels measured using Lumipulse G immunoassays.Methods
In this retrospective study, patients with dementia were recruited from an academic memory clinic (University Hospitals Leuven) based on the joint availability of an antemortem plasma sample and postmortem brain tissue. An N-terminal pTau217 (pTau217NT) immunoassay was used to measure pTau217 in plasma and inferior temporal neocortex homogenates. In plasma, midregion pTau217 (pTau217Mid) and the pTau217Mid/Aβ₁₋₄₂ ratio were also measured. Generalized additive models and partial Spearman correlations were used to evaluate the relationship between blood and cortical pTau217. CIs were estimated using bootstrapping (5,000 iterations).Results
Thirty-two patients with dementia (mean age 66 [SD 10] years, 38% female) were included, of which 19 had an AD diagnosis and 13 had a diagnosis of frontotemporal lobar degeneration with either TDP-43 or tau inclusions, as determined at autopsy. Plasma pTau217NT, pTau217Mid, and the pTau217Mid/Aβ₁₋₄₂ ratios were strongly correlated with pTau217NT in the temporal cortex (partial Spearman ρ = 0.73-78, all p < 0.0001). However, models using plasma pTau217NT or the pTau217Mid/Aβ₁₋₄₂ ratio as independent variable provided a better fit to cortical pTau217NT than models using plasma pTau217Mid (ΔAkaike information criterion = 2.5 and 1.1, ΔBayesian Information criterion = 3.6 and 2.1, respectively). All markers showed excellent diagnostic performance in distinguishing AD patients from non-AD disease control patients (area under the curve = 0.88-0.94). Plasma pTau217NT, pTau217Mid, and the pTau217Mid/Aβ₁₋₄₂ ratios were correlated with neocortical Aβ plaque (4G8) of pTau (AT8) aggregate densities with comparable strength (partial Spearman ρ = 0.57-0.69, p < 0.0012). For all plasma markers studied, only the correlation with pTau aggregate density (partial Spearman ρ = 0.39-0.45, p < 0.05) and not with Aβ plaque density (partial partial Spearman ρ = 0.17-0.25, p > 0.19) remained significant after correction for the other pathology.Discussion
Plasma pTau217NT levels as well as the pTau217Mid/Aβ₁₋₄₂ ratio strongly relate to postmortem pTau217NT levels in the temporal cortex.
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BibTeX
@article{meyer2026quantitative,
title = {{Quantitative Relationship Between Lumipulse G Measures of pTau217 in Plasma and the Temporal Cortex.}},
author = {Steffi De Meyer and Sandra O Tomé and Bas Lahaije and Jeroen Vanbrabant and Charlotte Lambrechts and Julie Goossens and Eugeen Vanmechelen and Kristel Sleegers and Christine A F Von Arnim and Thomas Tousseyn and Koen Poesen and Dietmar Rudolf Thal and Rik Vandenberghe},
journal = {Neurology},
year = {2026},
month = oct,
doi = {10.1212/wnl.0000000000218598},
url = {https://europepmc.org/article/MED/42837647},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Quantitative Relationship Between Lumipulse G Measures of pTau217 in Plasma and the Temporal Cortex.
AU - Steffi De Meyer
AU - Sandra O Tomé
AU - Bas Lahaije
AU - Jeroen Vanbrabant
AU - Charlotte Lambrechts
AU - Julie Goossens
AU - Eugeen Vanmechelen
AU - Kristel Sleegers
AU - Christine A F Von Arnim
AU - Thomas Tousseyn
AU - Koen Poesen
AU - Dietmar Rudolf Thal
AU - Rik Vandenberghe
PY - 2026
DA - 2026/10/05
JO - Neurology
DO - 10.1212/wnl.0000000000218598
UR - https://europepmc.org/article/MED/42837647
AB - Background and objectives Phosphorylated tau217 (pTau217) plasma assays have shown high diagnostic accuracy for Alzheimer disease (AD). However, validation of plasma pTau217 as a direct marker of brain-based pTau pathology requires understanding of its quantitative relationship with cortical pTau217. The primary objective of this postmortem validation study was to determine the quantitative relationship of plasma pTau217 levels and the pTau217/β-amyloid (Aβ)₁₋₄₂ ratio with cortical pTau217 levels measured using Lumipulse G immunoassays.Methods In this retrospective study, patients with dementia were recruited from an academic memory clinic (University Hospitals Leuven) based on the joint availability of an antemortem plasma sample and postmortem brain tissue. An N-terminal pTau217 (pTau217NT) immunoassay was used to measure pTau217 in plasma and inferior temporal neocortex homogenates. In plasma, midregion pTau217 (pTau217Mid) and the pTau217Mid/Aβ₁₋₄₂ ratio were also measured. Generalized additive models and partial Spearman correlations were used to evaluate the relationship between blood and cortical pTau217. CIs were estimated using bootstrapping (5,000 iterations).Results Thirty-two patients with dementia (mean age 66 [SD 10] years, 38% female) were included, of which 19 had an AD diagnosis and 13 had a diagnosis of frontotemporal lobar degeneration with either TDP-43 or tau inclusions, as determined at autopsy. Plasma pTau217NT, pTau217Mid, and the pTau217Mid/Aβ₁₋₄₂ ratios were strongly correlated with pTau217NT in the temporal cortex (partial Spearman ρ = 0.73-78, all p < 0.0001). However, models using plasma pTau217NT or the pTau217Mid/Aβ₁₋₄₂ ratio as independent variable provided a better fit to cortical pTau217NT than models using plasma pTau217Mid (ΔAkaike information criterion = 2.5 and 1.1, ΔBayesian Information criterion = 3.6 and 2.1, respectively). All markers showed excellent diagnostic performance in distinguishing AD patients from non-AD disease control patients (area under the curve = 0.88-0.94). Plasma pTau217NT, pTau217Mid, and the pTau217Mid/Aβ₁₋₄₂ ratios were correlated with neocortical Aβ plaque (4G8) of pTau (AT8) aggregate densities with comparable strength (partial Spearman ρ = 0.57-0.69, p < 0.0012). For all plasma markers studied, only the correlation with pTau aggregate density (partial Spearman ρ = 0.39-0.45, p < 0.05) and not with Aβ plaque density (partial partial Spearman ρ = 0.17-0.25, p > 0.19) remained significant after correction for the other pathology.Discussion Plasma pTau217NT levels as well as the pTau217Mid/Aβ₁₋₄₂ ratio strongly relate to postmortem pTau217NT levels in the temporal cortex.
SN - 0028-3878
SN - 1526-632X
ER -