Iolanda Riba-Llena

Recent studies have demonstrated the high analytical and diagnostic performance of plasma p-tau217 using well-defined cohorts. We aimed to assess the analytical, diagnostic, and prognostic utility of plasma p-tau217 as a routine biomarker in symptomatic patients attending our memory clinic. We also sought to identify optimal cutoff points that align with cerebrospinal fluid (CSF) amyloid beta (Aβ) status. A total of 276 cognitively impaired patients were included, with 81 mild cognitive impairment (MCI) patients followed for a mean of 56 (±15.8) months to evaluate progression to Alzheimer’s disease (AD). CSF and blood biomarkers of AD were quantified using the Lumipulse G platform. Plasma p-tau217 levels showed strong correlations with CSF Aβ42/Aβ40 (r = −0.707), p-tau181/Aβ42 (r = 0.842), and p-tau181 (r = 0.728). Plasma p-tau217 levels were significantly higher in the A + T + group than in A − T +/− (p < 0.001) and outperformed other plasma markers in detecting CSF Aβ pathology (AUC 0.924).Additionally, p-tau217 moderated cognitive changes over time as measured by the Mini-mental state examination (MMSE) (F(2, 70) = 13.995, p < 0.001) and outperformed other plasma biomarkers in predicting progression from MCI to AD (AUC 0.876). Using a dual cutoff strategy, 72% of patients were classified with 94.9% concordance with CSF Aβ status. Plasma p-tau217 shows strong potential as a non-invasive, cost-effective diagnostic and prognostic tool in clinical settings.

We compared the clinical and analytical performance of Alzheimer’s disease (AD) plasma biomarkers measured using the single-molecule array (Simoa) and Lumipulse platforms. We quantified the plasma levels of amyloid beta 42 (Aβ42), Aβ40, phosphorylated tau (Ptau181), and total tau biomarkers in 81 patients with mild cognitive impairment (MCI), 30 with AD, and 16 with non-AD dementia. We found a strong correlation between the Simoa and Lumipulse methods. Concerning the clinical diagnosis, Simoa Ptau181/Aβ42 (AUC 0.739, 95% CI 0.592–0.887) and Lumipulse Aβ42 and Ptau181/Aβ42 (AUC 0.735, 95% CI 0.589–0.882 and AUC 0.733, 95% CI 0.567–0.900) had the highest discriminating power. However, their power was significantly lower than that of CSF Aβ42/Aβ40, as measured by Lumipulse (AUC 0.879, 95% CI 0.766–0.992). Simoa Ptau181 and Lumipulse Ptau181/Aβ42 were the markers most consistent with the CSF Aβ42/Aβ40 status (AUC 0.801, 95% CI 0.712–0.890 vs. AUC 0.870, 95% CI 0.806–0.934, respectively) at the ≥2.127 and ≥0.084 cut-offs, respectively. The performance of the Simoa and Lumipulse plasma AD assays is weaker than that of CSF AD biomarkers. At present, the analysed AD plasma biomarkers may be useful for screening to reduce the number of lumbar punctures in the clinical setting.