Journal of Alzheimer’s Disease | October 13, 2020

Triana-Baltzer G, Van Kolen K, Theunis C, Moughadam S, Slemmon R, Mercken M, Galpern W, Sun H and Kolb H

Journal of Alzheimer’s disease : JAD. 2020;77:1417-1430

DOI: 10.3233/JAD-200463

This study was performed using Simoa Homebrew Assays.

Abstract

Background:

Early and accurate detection and staging is critical to managing Alzheimer’s disease (AD) and supporting clinical trials. Cerebrospinal fluid (CSF) biomarkers for amyloid-β peptides, tau species, and various neurodegenerative and inflammatory analytes are leading the way in this regard, yet there is room for improved sensitivity and specificity. In particular tau is known to be present in many different fragments, conformations, and post-translationally modified forms. While the exact tau species that might best reflect AD pathology is unknown, a growing body of evidence suggests that forms with high levels of phosphorylation in the mid-region may be especially enriched in AD.

Objective:

Develop an assay for measuring p217tau in CSF.

Methods:

Here we describe the development and validation of a novel sELISA for measuring CSF tau species containing phosphorylation at threonines 212 & 217, aka p217 + tau, using the PT3 antibody.

Results:

While the analyte is present at extremely low levels the assay is sufficiently sensitive and specific to quantitate p217 + tau with excellent precision, accuracy, and dilution linearity, allowing good differentiation between diagnostic subgroups. The p217 + tau measurements appear to track AD pathology better than the commonly used p181tau epitope, suggesting superior diagnostic and staging performance. Finally, the assay can also be configured to differentiate antibody-bound versus antibody-free tau, and therefore can be used to measure target engagement by p217 + tau-targeting immunotherapeutics.

Conclusion:

The assay for measuring p217 + tau described here is highly sensitive, accurate, precise, dilution linear, and shows good potential for identifying and staging AD.

This study was performed using the Quanterix HD-1 Analyzer.