Clinical Value of Plasma pTau217 Immunoassay for Assessing Alzheimer's Disease

This research explores the clinical value of plasma phosphorylated tau proteins (p-tau) 217 and 181 in assessing patients with mild cognitive impairment. Mild cognitive impairment may be a precursor stage of Alzheimer’s disease (AD), and early detection and monitoring of disease progression are crucial for disease management.

Research Background:

Alzheimer’s disease patients produce β-amyloid protein (Aβ) deposits and tau protein pathological changes in their bodies, causing cognitive function to gradually deteriorate. Detection of these biomarkers can help diagnose and predict disease progression. Recent research shows that plasma p-tau217 has more potential to become a good biomarker for AD than p-tau181. However, its clinical application still needs to be verified in prospective cohorts and assess potential influencing factors.

Research Process:

This study comes from the BALTAZAR (Biomarker of Amyloid peptide and Alzheimer’s disease risk) multi-center cohort in France, including 473 patients with mild cognitive impairment, with an average age of 77.7 years, tracked for 3 years. Using Quanterix and AlzPath’s SIMOA detection technology, patient’s plasma p-tau181 and p-tau217 levels were determined. Patients were divided into Aβ-positive (brain deposits of Aβ) and negative groups according to the cerebrospinal fluid Aβ42/40 ratio. Patients’ transition to Alzheimer’s disease was tracked, and the impact of other biomarkers on p-tau was evaluated.

Main Research Results: 1. The p-tau217 and 181 levels in the Aβ-positive group (55%) were 2.7 and 1.5 times higher than the negative group, respectively. 2. The p-tau217 and 181 levels in patients who transitioned to AD were 70% and 30% higher than the non-transitioned group, respectively. 3. The area under the ROC curve for determining Aβ-positive status, p-tau217 (0.914) was significantly higher than p-tau181 (0.783). 4. The area under the ROC curve for predicting a shift to AD, p-tau217 (0.746) was slightly higher than p-tau181 (0.677). 5. In the Cox risk model, p-tau217 (hazard ratio 8.30) had a stronger predictive capability for transitioning to AD than p-tau181 (hazard ratio 1.38). 6. Plasma p-tau217 is associated with age, APOEε4 and renal function abnormalities, but these factors have a limited effect on its diagnostic performance. 7. When p-tau217 > 0.8pg/ml, there is a 95% positive predictive value for determining Aβ-positive; < 0.23pg/ml, there is a 95% negative predictive value for determining negative. At these two thresholds, the ratios for transitioning to AD were 56.8% and 9.7%, respectively.

Research Significance: 1. This is the first evaluation of AlzPath’s p-tau217 SIMOA assay kit’s clinical performance in a cohort of patients with mild cognitive impairment. 2. It confirms that p-tau217 is superior to p-tau181 in detecting brain Aβ deposition status, predicting cognitive decline, and transitioning to AD. 3. It provides useful threshold references for applying p-tau217 in clinical practice. 4. It’s beneficial to optimize the diagnostic strategy, prevention, and obtain disease modifications for Alzheimer’s patients.

Research Highlights: 1. A large-scale prospective cohort study, with research subjects being clinically common patients with mild cognitive impairment. 2. For the first time, potential influencing factors (such as age, genetics, comorbidities) on p-tau217 diagnostic performance were systematically evaluated. 3. The specific application scheme of p-tau217 detection in clinical diagnostic and therapeutic pathways is proposed.

This research provides solid evidence-based medicine support for the application of the p-tau217 biomarker in clinical practice and will have a significant impact on improving the early detection and precision management of Alzheimer’s disease.