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Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer's disease

Artikel i vetenskaplig tidskrift
Författare Karl Hansson
Rahil Dahlén
O. Hansson
Elin Pernevik
R. Paterson
J. M. Schott
N. Magdalinou
Henrik Zetterberg
Kaj Blennow
Johan Gobom
Publicerad i Clinical Mass Spectrometry
Volym 14
Sidor 74-82
ISSN 2376-9998
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 74-82
Språk en
Länkar dx.doi.org/10.1016/j.clinms.2019.07...
Ämnesord AD, Microtubule-associated protein tau, Endogenous peptides, Biomarker, Peptidomics, Mass spectrometry, cerebrospinal-fluid, phosphorylated-tau, criteria, quantification, threonine-181, biomarkers
Ämneskategorier Neurovetenskaper

Sammanfattning

Cerebrospinal fluid (CSF) tau and phospho-tau are well established biomarkers of Alzheimer's disease. While these measures are conventionally referred to as 'total tau' (T-tau) and 'phospho-tau' (P-tau), several truncated and modified tau forms exist that may relay additional diagnostic information. We evaluated the diagnostic performance of an endogenous tau peptide in CSF, tau 175-190, in the phosphorylated and non-phosphorylated state. A liquid chromatography-mass spectrometry (LC-MS) method was established to measure these peptides in CSF and was used to analyze two independent clinical cohorts; the first cohort included patients with Alzheimer's disease (AD, n = 15), Parkinson's disease (PD, n = 15), progressive supranuclear palsy (PSP, n = 15), and healthy controls (n = 15), the second cohort included AD patients (n = 16), and healthy controls (n = 24). In both cohorts T-tau and P-tau concentrations were determined by immunoassay. While tau 175-190 and P-tau 175-190 did not differentiate the study groups, the separation of AD and controls by T-tau (area under the ROC Curve (AUC) = 95%) and P-tau (AUC = 92%) was improved when normalizing the ELISA measurements to the concentrations of the endogenous peptides: T-tau/tau 175-190 (AUC = 100%), P-tau/P-tau 175-190 (AUC = 95%). The separation between patients and controls by T-tau (AUC = 88%) and P-tau (AUC = 82%) was similarly improved in the second cohort by taking the ratios of T-tau/tau 175-190 (AUC = 97%) and P-tau/P-tau 175-190 (AUC = 98%). In conclusion, our results suggest that the performance of the AD biomarkers T-tau and P-tau could be improved by normalizing their measurements to the endogenous peptides tau 175-190 and P-tau 175-190, possibly because these endogenous tau peptides serve to normalize for physiological, and disease-independent, secretion of tau from neurons to the extracellular space and the CSF. Finally, the observations made here add to the general applicability of mass spectrometry as a tool for rapid identification and accurate quantification of biomarker candidates. (C) 2019 The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL). Published by Elsevier B.V. All rights reserved.

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