Abstract Details

Title An Ultrasensitive Immunoassay for the Detection of p-tau231 in Plasma, Serum & CSF

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-005

Objective

Develop a high-sensitivity Phospho-tau231 (p-tau231) assay using Simoa technology. Evaluate its performances in the detection of Alzheimer’s Disease (AD) and differentiation from other types of dementia.

Background Blood levels of p-tau231 increase prior to Aβ PET threshold attainment and Tau deposition during early phases of AD and are significantly associated with CSF and PET biomarkder of AD . Therefore, a high sensitivity p-tau231 assay could become a valuable tool for early AD diagnostics, research, drug discovery and drug efficacy monitoring.

Design/Methods A bead-based digital Simoa immunoassay was developed to detect p-tau231 in human serum, plasma, and CSF (n=10/matrix). Conditions were optimized for maximal sensitivity and analytical performance. The assay was evaluated for sensitivity, dilution linearity, cross-reactivity to total Tau and other phosphorylated Tau, spike recovery, and analyte detectability in normal human serum, plasma, and CSF. Disease differentiation was evaluated in plasma of 9 AD patients and age-matched healthy controls (HC).

Results

Assay LLOD 0.018 pg/mL; LLOQ: 0.029 pg/mL (all matrixes); Quantifiability: 100% of samples above LLOQ (all matrixes). Cross reactivity: 0.13% to total tau; 0.14%-1.6% to other types of p-tau. Linearity of sample dilution: plasma 82.6% AVE (81.7%-136.7% range), CSF 84.6% AVE (79.9%-92.2% range). Recovery of sample spike: Plasma 87.4% AVE (78.6%-94.9% range); CSF 111.3% AVE (102.3%-117.9% range).

The mean p-tau231 concentration was significantly higher in AD patients than in the age matched healthy controls ( AVE 0.193 pg/ml in AD versus 0.069 pg/ml in HC, p< 0.0001). Further characterization is underway.

Conclusions The new Simoa p-tau231 assay provides a highly sensitive, specific, and robust tool for the measurement of this biomarker in plasma and CSF samples. Efforts are underway to make this assay widely available as a new tool to facilitate research in AD and other neurodegenerative diseases. Studies on a larger cohort of clinical samples is underway and will further determine its clinical utility.

Authors/Disclosures
Valerie Brachet, PhD (Fluxus inc.) PRESENTER	Dr. Brachet has received personal compensation for serving as an employee of Fluxus inc..
	No disclosure on file

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