PLASMA p-tau217 testing can achieve higher diagnostic accuracy and improved cost efficiency for amyloid beta detection when biologically informed cutoffs are applied rather than a standard single threshold, according to a large multicentre cohort study.
Plasma p-tau217 and Biological Variation
Plasma p-tau217 is increasingly used to detect amyloid beta pathology but concentrations vary with biological factors including kidney function, body mass index, and anaemia. The study evaluated whether adapting decision thresholds to these biological subgroups or applying a double cutoff strategy could outperform the standard single cutoff approach for identifying amyloid beta positivity.
Researchers analysed data from a multicentre cross sectional cohort study conducted between 2016–2023 with analyses completed in 2025. All participants underwent amyloid positron emission tomography imaging alongside plasma p-tau217 testing and clinical evaluation. Kidney function, body mass index, and haemoglobin were assessed to define subgroups including chronic kidney disease, underweight, obesity, and anaemia.
Diagnostic Accuracy Across Subgroups
Across cohorts, subgroup specific optimal cutoffs consistently improved diagnostic accuracy compared with the standard single cutoff. Gains were most pronounced in participants with chronic kidney disease and anaemia. In one cohort, accuracy in chronic kidney disease increased from 0.65; 95% CI:0.57–0.72 to 0.83; 95% CI:0.76–0.89, while accuracy in anaemia rose from 0.80; 95% CI:0.76–0.84 to 0.86; 95% CI:0.82–0.90. Similar patterns were observed across testing platforms.
A double cutoff strategy also improved accuracy and reduced false positive and false negative classifications across all biological subgroups. However, this approach generated intermediate results in 12–39% of cases, requiring further confirmatory imaging.
Cost Efficiency and Clinical Implications
When directly compared, biologically optimised cutoffs provided similar or better accuracy than the double cutoff strategy in chronic kidney disease while lowering total diagnostic costs by reducing the need for additional imaging. In anaemia, the double cutoff delivered marginally higher accuracy but required confirmatory imaging in up to 25% of cases, diminishing its economic advantage. In obesity, the double cutoff remained superior for both diagnostic performance and cost efficiency.
These findings suggest that biologically optimised plasma p-tau217 thresholds may represent a balanced and cost-effective default strategy for amyloid beta detection, particularly in patients with chronic kidney disease or anaemia, while double cutoff approaches may still be preferable in obesity.
Reference
Yun J et al. Plasma phosphorylated tau 217 cutoffs for amyloid pathology and kidney function, body mass index, and anemia. JAMA Neurol. 2026; doi: 10.1001/jamaneurol.2025.5530.
