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Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome
IMPORTANCE: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071401/ https://www.ncbi.nlm.nih.gov/pubmed/37010841 http://dx.doi.org/10.1001/jamaneurol.2023.0488 |
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author | VandeVrede, Lawren La Joie, Renaud Thijssen, Elisabeth H. Asken, Breton M. Vento, Stephanie A. Tsuei, Torie Baker, Suzanne L. Cobigo, Yann Fonseca, Corrina Heuer, Hilary W. Kramer, Joel H. Ljubenkov, Peter A. Rabinovici, Gil D. Rojas, Julio C. Rosen, Howie J. Staffaroni, Adam M. Boeve, Brad F. Dickerson, Brad C. Grossman, Murray Huey, Edward D. Irwin, David J. Litvan, Irene Pantelyat, Alexander Y. Tartaglia, Maria Carmela Dage, Jeffrey L. Boxer, Adam L. |
author_facet | VandeVrede, Lawren La Joie, Renaud Thijssen, Elisabeth H. Asken, Breton M. Vento, Stephanie A. Tsuei, Torie Baker, Suzanne L. Cobigo, Yann Fonseca, Corrina Heuer, Hilary W. Kramer, Joel H. Ljubenkov, Peter A. Rabinovici, Gil D. Rojas, Julio C. Rosen, Howie J. Staffaroni, Adam M. Boeve, Brad F. Dickerson, Brad C. Grossman, Murray Huey, Edward D. Irwin, David J. Litvan, Irene Pantelyat, Alexander Y. Tartaglia, Maria Carmela Dage, Jeffrey L. Boxer, Adam L. |
author_sort | VandeVrede, Lawren |
collection | PubMed |
description | IMPORTANCE: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. OBJECTIVE: To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. DESIGN, SETTING, AND PARTICIPANTS: This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. MAIN OUTCOME AND MEASURES: Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. RESULTS: Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). CONCLUSIONS AND RELEVANCE: In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials. |
format | Online Article Text |
id | pubmed-10071401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-100714012023-04-05 Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome VandeVrede, Lawren La Joie, Renaud Thijssen, Elisabeth H. Asken, Breton M. Vento, Stephanie A. Tsuei, Torie Baker, Suzanne L. Cobigo, Yann Fonseca, Corrina Heuer, Hilary W. Kramer, Joel H. Ljubenkov, Peter A. Rabinovici, Gil D. Rojas, Julio C. Rosen, Howie J. Staffaroni, Adam M. Boeve, Brad F. Dickerson, Brad C. Grossman, Murray Huey, Edward D. Irwin, David J. Litvan, Irene Pantelyat, Alexander Y. Tartaglia, Maria Carmela Dage, Jeffrey L. Boxer, Adam L. JAMA Neurol Original Investigation IMPORTANCE: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. OBJECTIVE: To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. DESIGN, SETTING, AND PARTICIPANTS: This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. MAIN OUTCOME AND MEASURES: Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. RESULTS: Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). CONCLUSIONS AND RELEVANCE: In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials. American Medical Association 2023-04-03 2023-05 /pmc/articles/PMC10071401/ /pubmed/37010841 http://dx.doi.org/10.1001/jamaneurol.2023.0488 Text en Copyright 2023 VandeVrede L et al. JAMA Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation VandeVrede, Lawren La Joie, Renaud Thijssen, Elisabeth H. Asken, Breton M. Vento, Stephanie A. Tsuei, Torie Baker, Suzanne L. Cobigo, Yann Fonseca, Corrina Heuer, Hilary W. Kramer, Joel H. Ljubenkov, Peter A. Rabinovici, Gil D. Rojas, Julio C. Rosen, Howie J. Staffaroni, Adam M. Boeve, Brad F. Dickerson, Brad C. Grossman, Murray Huey, Edward D. Irwin, David J. Litvan, Irene Pantelyat, Alexander Y. Tartaglia, Maria Carmela Dage, Jeffrey L. Boxer, Adam L. Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome |
title | Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome |
title_full | Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome |
title_fullStr | Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome |
title_full_unstemmed | Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome |
title_short | Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome |
title_sort | evaluation of plasma phosphorylated tau217 for differentiation between alzheimer disease and frontotemporal lobar degeneration subtypes among patients with corticobasal syndrome |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071401/ https://www.ncbi.nlm.nih.gov/pubmed/37010841 http://dx.doi.org/10.1001/jamaneurol.2023.0488 |
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