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PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations that are Used with Plasma Amyloid-β42/40 in a Multiple Analyte Assay with Algorithm for Detecting Brai
Eastwood, S.M.; Meyer, M.R.; Kirmess, K.M.; Wente-Roth, T.L.; Irvin, F.; Holubasch, M.S.; Verghese, P.B.; West, T.; Braunstein, J.B.; Yarasheski, K.E.; Contois, J.H. PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-β42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology. Diagnostics2024, 14, 1739.
Eastwood, S.M.; Meyer, M.R.; Kirmess, K.M.; Wente-Roth, T.L.; Irvin, F.; Holubasch, M.S.; Verghese, P.B.; West, T.; Braunstein, J.B.; Yarasheski, K.E.; Contois, J.H. PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-β42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology. Diagnostics 2024, 14, 1739.
Eastwood, S.M.; Meyer, M.R.; Kirmess, K.M.; Wente-Roth, T.L.; Irvin, F.; Holubasch, M.S.; Verghese, P.B.; West, T.; Braunstein, J.B.; Yarasheski, K.E.; Contois, J.H. PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-β42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology. Diagnostics2024, 14, 1739.
Eastwood, S.M.; Meyer, M.R.; Kirmess, K.M.; Wente-Roth, T.L.; Irvin, F.; Holubasch, M.S.; Verghese, P.B.; West, T.; Braunstein, J.B.; Yarasheski, K.E.; Contois, J.H. PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-β42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology. Diagnostics 2024, 14, 1739.
Abstract
Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.
Biology and Life Sciences, Neuroscience and Neurology
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