Work

Diagnostic performance of plasma pTau217/Aβ42 ratio and a three-zone threshold model for Alzheimer’s disease

Year: 2025

Type: article

Abstract: Early and accurate diagnosis of Alzheimer’s disease (AD) typically relies on invasive or expensive methods like cerebrospinal fluid (CSF) biomarkers and amyloid PET imaging. Blood-based biomarkers, particularly plasma phosphorylated tau (pTau 181 , pTau 217 ) and amyloid-beta ratios (Aβ 42 / 40 ), offer a more accessible diagnostic alternative. This study assessed the diagnostic accuracy of plasma biomarkers and developed a three-zone classification model to reduce reliance on invasive confirmatory tests. We retrospectively evaluated 109 participants referred to a tertiary memory clinic. Participants underwent cognitive assessments, brain MRI, CSF biomarker analyses (pTau 181 , Aβ 42 / 40 ), and plasma biomarker measurements (pTau 181 , pTau 217 , Aβ 42 / 40 , pTau 217 /Aβ 42 ratio). Diagnostic performance was evaluated using ROC analyses, and thresholds achieving ≥95% sensitivity and specificity were used to define low, intermediate and high-risk zones. Plasma biomarkers correlated significantly with CSF biomarkers. For identifying AD pathology (A+/T+ vs. others), plasma pTau 217 and the pTau 217 /Aβ 42 ratio demonstrated the highest accuracy (both AUC=0.95), outperforming plasma pTau 181 (AUC=0.88) and Aβ 42 / 40 ratio (AUC=0.73). At optimal thresholds, plasma pTau 217 showed 87.5% sensitivity and 93.4% specificity, whereas the pTau 217 /Aβ 42 ratio showed higher sensitivity (95.8%) but lower specificity (85.2%). Using the three-zone model, plasma pTau 217 enabled definitive classification in 80.7% of patients, increasing to 84.4% with the pTau 217 /Aβ 42 ratio. Among patients with mild cognitive impairment, plasma pTau 217 achieved excellent accuracy (AUC=0.98). Plasma pTau 217 , alone or combined with Aβ 42 , provides highly accurate and scalable identification of AD pathology, substantially reducing the need for invasive diagnostic procedures. • Plasma pTau 217 accurately detects CSF-defined Alzheimer’s pathology. • pTau 217 /Aβ 42 ratio reduces intermediate grey-zone classifications. • Three-zone model classifies over 80% of patients without CSF or amyloid PET. • Plasma biomarkers show strong correlations with CSF Aβ 42 / 40 and pTau 181 . • Plasma pTau 217 performs excellently in mild cognitive impairment (CDR 0.5).

Source: Neurobiology of Aging

DOI: 10.1016/j.neurobiolaging.2025.12.005