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Updated: Sep 24, 2025
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Phospho-specific plasma p-tau181 assay detects clinical as well as asymptomatic Alzheimer's disease
Steffi De Meyer1,2,3,4, Jeroen Vanbrabant5, Jolien M Schaeverbeke1,4
1Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Objective:
Plasma phosphorylated-tau-181 (p-tau181) reliably detects clinical Alzheimer's disease (AD) as well as asymptomatic amyloid-β (Aβ) pathology, but is consistently quantified with assays using antibody AT270, which cross-reacts with p-tau175. This study investigates two novel phospho-specific assays for plasma p-tau181 and p-tau231 in clinical and asymptomatic AD.
Methods:
Plasma p-tau species were quantified with Simoa in 44 AD patients, 40 spouse controls and an independent cohort of 151 cognitively unimpaired (CU) elderly who underwent Aβ-PET. Simoa plasma Aβ42 measurements were available in a CU subset (N = 69). Receiver operating characteristics and Aβ-PET associations were used to evaluate biomarker validity.
Results:
The novel plasma p-tau181 and p-tau231 assays did not show cross-reactivity. Plasma p-tau181 accurately detected clinical AD (area under the curve (AUC) = 0.98, 95% CI 0.95-1.00) as well as asymptomatic Aβ pathology (AUC = 0.84, 95% CI 0.76-0.92), while plasma p-tau231 did not (AUC = 0.74, 95% CI 0.63-0.85 and 0.61, 95% CI 0.52-0.71, respectively). Plasma p-tau181, but not p-tau231, detected asymptomatic Aβ pathology more accurately than age, sex and APOE combined (AUC = 0.64). In asymptomatic elderly, correlations between plasma p-tau181 and Aβ pathology were observed throughout the cerebral cortex (ρ = 0.40, p < 0.0001), with focal associations within AD-vulnerable regions, particularly the precuneus. The plasma Aβ42/p-tau181 ratio did not reflect asymptomatic Aβ pathology better than p-tau181 alone.
Interpretation:
The novel plasma p-tau181 assay is an accurate tool to detect clinical as well as asymptomatic AD and provides a phospho-specific alternative to currently employed immunoassays.
Insights
A new plasma assay for phosphorylated-tau-181 (p-tau181) accurately detects Alzheimer's disease (AD) and asymptomatic amyloid-β (Aβ) pathology. This phospho-specific tool offers a reliable alternative to existing immunoassays for AD biomarker detection.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Alzheimer's Disease Research
Background:
- Plasma phosphorylated-tau-181 (p-tau181) is a biomarker for Alzheimer's disease (AD) and amyloid-β (Aβ) pathology.
- Current assays for p-tau181 use antibody AT270, which has cross-reactivity with p-tau175, potentially affecting quantification accuracy.
- There is a need for novel, phospho-specific assays for accurate plasma p-tau quantification in AD.
Purpose of the Study:
- To investigate two novel phospho-specific assays for plasma p-tau181 and p-tau231.
- To evaluate the diagnostic and prognostic accuracy of these novel assays in clinical and asymptomatic AD.
- To assess the performance of novel plasma p-tau assays compared to existing methods and demographic factors.
Main Methods:
- Quantification of plasma p-tau species using Simoa technology in AD patients, spouse controls, and cognitively unimpaired (CU) elderly.
- Inclusion of a subset of CU individuals with available Simoa plasma Aβ42 measurements and Aβ-PET imaging.
- Evaluation of biomarker validity using receiver operating characteristic (ROC) analysis and associations with Aβ-PET.
Main Results:
- The novel plasma p-tau181 and p-tau231 assays demonstrated no cross-reactivity.
- Plasma p-tau181 accurately detected clinical AD (AUC=0.98) and asymptomatic Aβ pathology (AUC=0.84).
- Plasma p-tau181 showed superior performance in detecting asymptomatic Aβ pathology compared to age, sex, and APOE combined (AUC=0.64), with correlations observed in AD-vulnerable brain regions.
Conclusions:
- The novel plasma p-tau181 assay is a highly accurate tool for detecting both clinical and asymptomatic AD.
- This assay provides a phospho-specific and reliable alternative to current immunoassays for plasma p-tau181 quantification.
- The findings support the utility of plasma p-tau181 as a valuable biomarker in Alzheimer's disease research and diagnostics.
