Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease
Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217,...
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| Published in | The Journal of experimental medicine Vol. 217; no. 11 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Rockefeller University Press
02.11.2020
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms’ profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No correlation was found between CSF and plasma on total-tau levels and pS202 measures. We found p-tau-217 and p-tau-181 were highly specific for amyloid plaque pathology in the discovery cohort (n = 36, AUROC = 0.99 and 0.98 respectively). In the validation cohort (n = 92), p-tau-217 measures were still specific to amyloid status (AUROC = 0.92), and p-tau-181 measures were less specific (AUROC = 0.75). |
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| AbstractList | Highly sensitive and specific plasma biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms' profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No correlation was found between CSF and plasma on total-tau levels and pS202 measures. We found p-tau-217 and p-tau-181 were highly specific for amyloid plaque pathology in the discovery cohort (n = 36, AUROC = 0.99 and 0.98 respectively). In the validation cohort (n = 92), p-tau-217 measures were still specific to amyloid status (AUROC = 0.92), and p-tau-181 measures were less specific (AUROC = 0.75).Highly sensitive and specific plasma biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms' profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No correlation was found between CSF and plasma on total-tau levels and pS202 measures. We found p-tau-217 and p-tau-181 were highly specific for amyloid plaque pathology in the discovery cohort (n = 36, AUROC = 0.99 and 0.98 respectively). In the validation cohort (n = 92), p-tau-217 measures were still specific to amyloid status (AUROC = 0.92), and p-tau-181 measures were less specific (AUROC = 0.75). Highly sensitive and specific plasma biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms' profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No correlation was found between CSF and plasma on total-tau levels and pS202 measures. We found p-tau-217 and p-tau-181 were highly specific for amyloid plaque pathology in the discovery cohort (n = 36, AUROC = 0.99 and 0.98 respectively). In the validation cohort (n = 92), p-tau-217 measures were still specific to amyloid status (AUROC = 0.92), and p-tau-181 measures were less specific (AUROC = 0.75). Barthélemy et al. use mass spectrometry to characterize plasma tau isoforms and assess their diagnosis utility for Alzheimer’s disease. They demonstrate plasma tau phosphorylation measures of p-tau-217 and p-tau-181 are increased with amyloid. Their results support p-tau-217 is superior to p-tau-181 as an AD plasma biomarker. Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms’ profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No correlation was found between CSF and plasma on total-tau levels and pS202 measures. We found p-tau-217 and p-tau-181 were highly specific for amyloid plaque pathology in the discovery cohort ( n = 36, AUROC = 0.99 and 0.98 respectively). In the validation cohort ( n = 92), p-tau-217 measures were still specific to amyloid status (AUROC = 0.92), and p-tau-181 measures were less specific (AUROC = 0.75). |
| Author | Horie, Kanta Barthélemy, Nicolas R. Sato, Chihiro Bateman, Randall J. |
| AuthorAffiliation | 1 Department of Neurology, Washington University School of Medicine, St. Louis, MO 2 Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 3 Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO |
| AuthorAffiliation_xml | – name: 3 Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO – name: 1 Department of Neurology, Washington University School of Medicine, St. Louis, MO – name: 2 Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO |
| Author_xml | – sequence: 1 givenname: Nicolas R. orcidid: 0000-0003-4937-2860 surname: Barthélemy fullname: Barthélemy, Nicolas R. – sequence: 2 givenname: Kanta orcidid: 0000-0001-7736-2614 surname: Horie fullname: Horie, Kanta – sequence: 3 givenname: Chihiro orcidid: 0000-0002-7639-8727 surname: Sato fullname: Sato, Chihiro – sequence: 4 givenname: Randall J. orcidid: 0000-0002-7729-1702 surname: Bateman fullname: Bateman, Randall J. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32725127$$D View this record in MEDLINE/PubMed |
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| License | 2020 Barthelemy et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Disclosures: N.R. Barthélemy reported a patent to the US patent office for "blood-based assay for diagnosing and treating based on site-specific tau phosphorylation" pending, and a patent to the US patent office for "methods of diagnosing and treating based on site-specific tau phosphorylation" issued. Washington University and R.J. Bateman have equity ownership interest in C2N Diagnostics. R.J. Bateman and N.R. Barthélemy may receive royalty income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. R.J. Bateman receives income from C2N Diagnostics for serving on the scientific advisory board. K. Horie is a visiting scholar at Washington University and employed by Eisai Co., Ltd. K. Hori may receive income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. C. Sato may receive income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. R.J. Bateman reported "other" from C2N Diagnostics, personal fees from Eisai, AC Immune, Amgen, Pfizer, Hoffman LaRoche, and Janssen; and grants from AbbVie, Biogen, and Eli Lilly and Co. outside the submitted work. In addition, R.J. Bateman had a patent to "blood-based assay for diagnosing and treating based on site-specific tau phosphorylation" pending and a patent to "methods of diagnosing and treating based on site-specific tau phosphorylation" pending. Washington University and R.J. Bateman have equity ownership interest in C2N Diagnostics and may receive royalty income based on technology (methods of diagnosing AD with phosphorylation changes) pending license by Washington University to C2N Diagnostics. |
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| References | Mattsson (2023072622171225400_bib20) 2016; 87 Fagan (2023072622171225400_bib15) 2014; 6 Rubenstein (2023072622171225400_bib30) 2017; 74 Barthélemy (2023072622171225400_bib7) 2020; 26 Bateman (2023072622171225400_bib9) 2012; 367 2023072622171225400_bib4 Nakamura (2023072622171225400_bib23) 2018; 554 Preische (2023072622171225400_bib28) 2019; 25 Neselius (2023072622171225400_bib24) 2013; 27 Barthélemy (2023072622171225400_bib8) 2020; 12 Roberts (2023072622171225400_bib29) 2014; 76 Patterson (2023072622171225400_bib26) 2015; 78 Barthélemy (2023072622171225400_bib3) 2016; 15 Bulut (2023072622171225400_bib11) 2006; 23 Cicognola (2023072622171225400_bib12) 2019; 137 Barthélemy (2023072622171225400_bib2) 2015; 11 Janelidze (2023072622171225400_bib18) 2020; 11 Janelidze (2023072622171225400_bib17) 2020; 26 Fagan (2023072622171225400_bib14) 2007; 64 Tatebe (2023072622171225400_bib33) 2017; 12 Barthélemy (2023072622171225400_bib6) 2019; 11 Mielke (2023072622171225400_bib21) 2017; 74 Thijssen (2023072622171225400_bib34) 2020; 26 Potter (2023072622171225400_bib27) 2013; 5 Darlix (2023072622171225400_bib13) 2019; 19 Bacioglu (2023072622171225400_bib1) 2016; 91 Bogoslovsky (2023072622171225400_bib10) 2017; 34 Zetterberg (2023072622171225400_bib36) 2013; 5 Zetterberg (2023072622171225400_bib35) 2017; 43 Ovod (2023072622171225400_bib25) 2017; 13 Kasai (2023072622171225400_bib19) 2017; 12 Schindler (2023072622171225400_bib32) 2019; 93 Barthélemy (2023072622171225400_bib5) 2018; 14 Geyer (2023072622171225400_bib16) 2017; 13 Sato (2023072622171225400_bib31) 2018; 97 Mielke (2023072622171225400_bib22) 2018; 14 32792665 - Nat Rev Neurol. 2020 Oct;16(10):521 |
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| Snippet | Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate... Highly sensitive and specific plasma biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate... Barthélemy et al. use mass spectrometry to characterize plasma tau isoforms and assess their diagnosis utility for Alzheimer’s disease. They demonstrate plasma... |
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| SubjectTerms | Adult Aged Aged, 80 and over Alzheimer Disease - blood Alzheimer Disease - cerebrospinal fluid Alzheimer Disease - diagnostic imaging Alzheimer Disease - pathology Amyloid beta-Peptides - blood Amyloid beta-Peptides - cerebrospinal fluid Biomarkers - blood Brain - diagnostic imaging Brain - pathology Brief Definitive Report Case-Control Studies Cohort Studies Female Humans Male Mass Spectrometry - methods Middle Aged Neuroscience Phosphorylation Plaque, Amyloid Positron-Emission Tomography Protein Isoforms tau Proteins - blood tau Proteins - cerebrospinal fluid tau Proteins - chemistry |
| Title | Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease |
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