Blood-based Quantitation of p-Tau Proteins, BD-tau, and Inflammatory Cytokines in Alzheimer’s Disease
Ahmed Chenna1, Brandon Yee1, Melissa Grigsby2, Christos Petropoulos1
1R&D, Labcorp-Monogram Biosciences Inc, 2Quanterix Corp
Objective:
To evaluate and validate SIMOA (Quanterix) assays for p-Tau217, p-Tau181, p-Tau205, p-Tau212, BD-Tau, and inflammatory cytokines (IL-1β, IL-6, IL-10, TNFα) using plasma from Alzheimer’s disease (AD) patients compared with healthy controls, and to assess correlative relationships among these biomarkers.
Background:

Plasma levels of phosphorylated tau proteins (p-Tau217, p-Tau181, p-Tau205, p-Tau212), BD-Tau, and inflammatory cytokines are elevated in AD patients relative to healthy subjects. These biomarkers reflect amyloid plaque and tau neurofibrillary tangle pathology, neuronal injury, and inflammation, and are being investigated as diagnostic and prognostic tools for AD.

Design/Methods:

Plasma samples from AD patients (n=100) and healthy controls (n=75) were analyzed using SIMOA® p-Tau217, p-Tau181, p-Tau205, p-Tau212, BD-Tau, and cytokine 4-Plex A (IL-1β, IL-6, IL-10, TNFα) immunoassays, as well as the Lumipulse (Fujirebio) p-Tau217 assay. AD cases were selected based on a validated Fujirebio p-Tau217 cutoff >0.18 pg/mL, consistent with AD-related amyloid pathology.

Results:

Median levels of all nine SIMOA-based biomarkers and Lumipulse p-Tau217 were significantly elevated in AD plasma relative to controls (p<0.0001). Diagnostic performance was high across assays: SIMOA p-Tau217 (AUC=0.973), Lummipulse p-Tau217 (AUC=0.953), p-Tau181, p-Tau212, p-Tau205, BD-Tau, IL-1β, IL-6, IL-10, and TNFα (AUC=0.808–0.964). Strong correlations were observed between SIMOA and Lumipulse p-Tau217 (r=0.919), and between p-Tau217 and BD-Tau, p-Tau181, p-Tau212, and p-Tau205 (r=0.532–0.888). Cytokines IL-1β, IL-6, IL-10, and TNFα were also moderately to strongly intercorrelated (r=0.502–0.829).

Conclusions:

Blood biomarkers reflecting both neurodegeneration and inflammation were significantly elevated in AD plasma. Combined measurement of tau isoforms, BD-Tau, and inflammatory cytokines provides a practical diagnostic opportunity for identifying AD patients using minimally invasive blood samples.

10.1212/WNL.0000000000216629
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.