Validation of Plasma p-tau217 as a Biomarker of Prodromal Alzheimer's Disease.

BACKGROUND

Plasma phosphorylated tau 217 protein (p-tau217p) has recently been proposed as a useful biomarker for the early diagnosis of Alzheimer's disease (AD). However, local validation is recommended because of the potential influence of clinical, analytical, and preanalytical factors on assay performance.

METHODS

Between 2021 and 2024, we evaluated patients with amnestic mild cognitive impairment (aMCI) through clinical history, neurological and neuropsychological examination, blood sampling for biobanking, brain imaging, and lumbar puncture, among other diagnostic tests. In September 2025, p-tau217p levels were measured simultaneously using the LUMIPULSE immunoassay (Fujirebio). The diagnostic validity, reproducibility, receiver operating characteristic (ROC) curve performance, correlation with cerebrospinal fluid (CSF) biomarkers, and influence of clinical and analytical variables were evaluated in this study.

RESULTS

Among the 108 aMCI patients included, 66 met the criteria for clinic-biological AD, while the remainder had alternative clinical diagnoses. Using a two-threshold approach, p-tau217p levels ≥0.19 yielded a sensitivity of 88% and a positive predictive value of 83% for identifying AD. Levels ≥0.39 showed a specificity of 91% and a positive predictive value of 90% for the same purpose. Intermediate values (0.20-0.38) achieved a specificity of 83%. The intraclass correlation coefficient for the assay reproducibility was 0.97. The ROC curve for p-tau217p demonstrated an area under the curve of 0.86 for diagnosing AD. P-tau217p correlated more strongly with CSF p-tau181 (ρ = 0.63; p < 0.01) than with CSF Aβ1-42 (ρ = -0.40; p < 0.01). Finally, a reduced glomerular filtration rate was associated with a significant increase in p-tau217p levels (p < 0.006).

CONCLUSIONS

In our setting, p-tau217p measurement showed a high validity for the diagnosis of prodromal AD, which is consistent with the recent neurological literature. The assay showed high reproducibility, although results may be influenced by renal function. P-tau217p correlated more strongly with CSF p-tau181 than with CSF Aβ1-42.