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Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer’s disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathol...

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Autores principales: Milà-Alomà, Marta, Ashton, Nicholas J., Shekari, Mahnaz, Salvadó, Gemma, Ortiz-Romero, Paula, Montoliu-Gaya, Laia, Benedet, Andrea L., Karikari, Thomas K., Lantero-Rodriguez, Juan, Vanmechelen, Eugeen, Day, Theresa A., González-Escalante, Armand, Sánchez-Benavides, Gonzalo, Minguillon, Carolina, Fauria, Karine, Molinuevo, José Luis, Dage, Jeffrey L., Zetterberg, Henrik, Gispert, Juan Domingo, Suárez-Calvet, Marc, Blennow, Kaj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499867/
https://www.ncbi.nlm.nih.gov/pubmed/35953717
http://dx.doi.org/10.1038/s41591-022-01925-w
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author Milà-Alomà, Marta
Ashton, Nicholas J.
Shekari, Mahnaz
Salvadó, Gemma
Ortiz-Romero, Paula
Montoliu-Gaya, Laia
Benedet, Andrea L.
Karikari, Thomas K.
Lantero-Rodriguez, Juan
Vanmechelen, Eugeen
Day, Theresa A.
González-Escalante, Armand
Sánchez-Benavides, Gonzalo
Minguillon, Carolina
Fauria, Karine
Molinuevo, José Luis
Dage, Jeffrey L.
Zetterberg, Henrik
Gispert, Juan Domingo
Suárez-Calvet, Marc
Blennow, Kaj
author_facet Milà-Alomà, Marta
Ashton, Nicholas J.
Shekari, Mahnaz
Salvadó, Gemma
Ortiz-Romero, Paula
Montoliu-Gaya, Laia
Benedet, Andrea L.
Karikari, Thomas K.
Lantero-Rodriguez, Juan
Vanmechelen, Eugeen
Day, Theresa A.
González-Escalante, Armand
Sánchez-Benavides, Gonzalo
Minguillon, Carolina
Fauria, Karine
Molinuevo, José Luis
Dage, Jeffrey L.
Zetterberg, Henrik
Gispert, Juan Domingo
Suárez-Calvet, Marc
Blennow, Kaj
author_sort Milà-Alomà, Marta
collection PubMed
description Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer’s disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer’s disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer’s disease clinical trials.
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spelling pubmed-94998672022-09-24 Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease Milà-Alomà, Marta Ashton, Nicholas J. Shekari, Mahnaz Salvadó, Gemma Ortiz-Romero, Paula Montoliu-Gaya, Laia Benedet, Andrea L. Karikari, Thomas K. Lantero-Rodriguez, Juan Vanmechelen, Eugeen Day, Theresa A. González-Escalante, Armand Sánchez-Benavides, Gonzalo Minguillon, Carolina Fauria, Karine Molinuevo, José Luis Dage, Jeffrey L. Zetterberg, Henrik Gispert, Juan Domingo Suárez-Calvet, Marc Blennow, Kaj Nat Med Brief Communication Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer’s disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer’s disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer’s disease clinical trials. Nature Publishing Group US 2022-08-11 2022 /pmc/articles/PMC9499867/ /pubmed/35953717 http://dx.doi.org/10.1038/s41591-022-01925-w Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Milà-Alomà, Marta
Ashton, Nicholas J.
Shekari, Mahnaz
Salvadó, Gemma
Ortiz-Romero, Paula
Montoliu-Gaya, Laia
Benedet, Andrea L.
Karikari, Thomas K.
Lantero-Rodriguez, Juan
Vanmechelen, Eugeen
Day, Theresa A.
González-Escalante, Armand
Sánchez-Benavides, Gonzalo
Minguillon, Carolina
Fauria, Karine
Molinuevo, José Luis
Dage, Jeffrey L.
Zetterberg, Henrik
Gispert, Juan Domingo
Suárez-Calvet, Marc
Blennow, Kaj
Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
title Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
title_full Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
title_fullStr Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
title_full_unstemmed Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
title_short Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
title_sort plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical alzheimer’s disease
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499867/
https://www.ncbi.nlm.nih.gov/pubmed/35953717
http://dx.doi.org/10.1038/s41591-022-01925-w
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