Real-life reliability of plasma pTau181, Aβ42/Aβ40, and pTau181/Aβ42 measured by Lumipulse G600II in predicting cerebrospinal fluid amyloid status

Background: Alzheimer's disease (AD) is the most common neurodegenerative dementia, with diagnosis traditionally reliant on clinical criteria. Cerebrospinal fluid (CSF) biomarkers like pTau181 and Aβ42/Aβ40 ratio significantly improve diagnostic accuracy but are invasive. Plasma biomarkers measured by automated assays offer a non-invasive alternative. Objective: To evaluate the diagnostic performance of plasma pTau181, Aβ42/Aβ40, and pTau181/Aβ42 ratios in predicting CSF amyloid status in a real-life clinical setting. Methods: Data from consecutive patients whose plasma and CSF samples sent to our laboratory between March and October 2022, were retrospectively analyzed. Plasma and CSF pTau181, Aβ42, and Aβ40 levels were measured using the Lumipulse G600II platform. CSF amyloid status was classified as amyloid-positive (A+) or amyloid-negative (A-) based on the Aβ42/Aβ40 ratio. Statistical analyses included Spearman correlation, receiver operating characteristic (ROC) curves, and multivariate logistic regression to evaluate biomarker performance. Results: Among 165 individuals (83 females), 29.1% were classified as A+. Significant correlations were found between plasma and CSF biomarkers, with the highest for the pTau181/Aβ42 ratio (ρ=0.620, p < 0.0001). ROC analysis showed the pTau181/Aβ42 ratio had the highest diagnostic performance (AUC 0.818), followed by pTau181 (AUC 0.794) and Aβ42/Aβ40 (AUC 0.775). Combining plasma biomarkers in age-adjusted models improved diagnostic accuracy (AUC up to 0.846). Conclusions: Plasma biomarkers measured by the Lumipulse G600II platform show strong potential in predicting CSF amyloid status and possibly reduces the need for lumbar punctures. These findings support the potential use of plasma assays in the early diagnosis of AD. Anyway, further validations in larger multicenter cohorts are mandatory.