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

Marta Milà-Alomà; Nicholas J. Ashton; Mahnaz Shekari; Gemma Salvadó; Paula Ortiz-Romero; Laia Montoliu-Gaya; Andrea L Benedet; Thomas K. Karikari; Juan Lantero-Rodriguez; Eugeen Vanmechelen; Theresa A. Day; Armand González-Escalante; Gonzalo Sánchez-Benavides; Carolina Minguillon; Karine Fauria; José Luis Molinuevo; Jeffrey L. Dage; Henrik Zetterberg; Juan Domingo Gispert; Marc Suárez-Calvet; Kaj Blennow

doi:10.1038/s41591-022-01925-w

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

Marta Milà-Alomà
, Nicholas J. Ashton
, Mahnaz Shekari
, Gemma Salvadó
, Paula Ortiz-Romero
, Laia Montoliu-Gaya
, Andrea L Benedet
, Thomas K. Karikari
, Juan Lantero-Rodriguez
, Eugeen Vanmechelen
, Theresa A. Day
, Armand González-Escalante
, Gonzalo Sánchez-Benavides
, Carolina Minguillon
, Karine Fauria
, José Luis Molinuevo
, Jeffrey L. Dage
, Henrik Zetterberg
, Juan Domingo Gispert
, Marc Suárez-Calvet^*

Kaj Blennow^*

^*Corresponding author for this work

Old Age Psychiatry

Pasqual Maragall Foundation
Servicio de Medicina Interna y Enfermedades Infecciosas, Hospital del Mar-IMIM and RETICEF
Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES)
Pompeu Fabra University
University of Gothenburg
ADx NeuroSciences NV
CIBER-BBN
Plataforma de Neuroimatge
Barcelonabeta Brain Research Center (BBRC)
Centro de Investigación Biomédica en Red Bioingeniería
BBRC Barcelonaβeta Brain Research Center

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Abstract

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.

Original language	English
Pages (from-to)	1797–1801
Number of pages	5
Journal	Nature Medicine
Volume	28
Early online date	11 Aug 2022
DOIs	https://doi.org/10.1038/s41591-022-01925-w
Publication status	Published - Sept 2022

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Milà-Alomà, M., Ashton, N. J., Shekari, M., Salvadó, G., Ortiz-Romero, P., Montoliu-Gaya, L., Benedet, A. L., Karikari, T. K., Lantero-Rodriguez, J., Vanmechelen, E., Day, T. A., González-Escalante, A., Sánchez-Benavides, G., Minguillon, C., Fauria, K., Molinuevo, J. L., Dage, J. L., Zetterberg, H., Gispert, J. D., ... Blennow, K. (2022). Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease. Nature Medicine, 28, 1797–1801. https://doi.org/10.1038/s41591-022-01925-w

@article{0409bfd53cf840e5a2a10cd9fbbdbca2,

title = "Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer{\textquoteright}s disease",

abstract = "Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer{\textquoteright}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{\textquoteright}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{\textquoteright}s disease clinical trials.",

author = "Marta Mil{\`a}-Alom{\`a} and Ashton, \{Nicholas J.\} and Mahnaz Shekari and Gemma Salvad{\'o} and Paula Ortiz-Romero and Laia Montoliu-Gaya and Benedet, \{Andrea L\} and Karikari, \{Thomas K.\} and Juan Lantero-Rodriguez and Eugeen Vanmechelen and Day, \{Theresa A.\} and Armand Gonz{\'a}lez-Escalante and Gonzalo S{\'a}nchez-Benavides and Carolina Minguillon and Karine Fauria and Molinuevo, \{Jos{\'e} Luis\} and Dage, \{Jeffrey L.\} and Henrik Zetterberg and Gispert, \{Juan Domingo\} and Marc Su{\'a}rez-Calvet and Kaj Blennow",

year = "2022",

month = sep,

doi = "10.1038/s41591-022-01925-w",

language = "English",

volume = "28",

pages = "1797–1801",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

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Milà-Alomà, M, Ashton, NJ, Shekari, M, Salvadó, G, Ortiz-Romero, P, Montoliu-Gaya, L, Benedet, AL, Karikari, TK, Lantero-Rodriguez, J, Vanmechelen, E, Day, TA, González-Escalante, A, Sánchez-Benavides, G, Minguillon, C, Fauria, K, Molinuevo, JL, Dage, JL, Zetterberg, H, Gispert, JD, Suárez-Calvet, M & Blennow, K 2022, 'Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease', Nature Medicine, vol. 28, pp. 1797–1801. https://doi.org/10.1038/s41591-022-01925-w

TY - JOUR

T1 - Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

AU - Milà-Alomà, Marta

AU - Ashton, Nicholas J.

AU - Shekari, Mahnaz

AU - Salvadó, Gemma

AU - Ortiz-Romero, Paula

AU - Montoliu-Gaya, Laia

AU - Benedet, Andrea L

AU - Karikari, Thomas K.

AU - Lantero-Rodriguez, Juan

AU - Vanmechelen, Eugeen

AU - Day, Theresa A.

AU - González-Escalante, Armand

AU - Sánchez-Benavides, Gonzalo

AU - Minguillon, Carolina

AU - Fauria, Karine

AU - Molinuevo, José Luis

AU - Dage, Jeffrey L.

AU - Zetterberg, Henrik

AU - Gispert, Juan Domingo

AU - Suárez-Calvet, Marc

AU - Blennow, Kaj

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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.

U2 - 10.1038/s41591-022-01925-w

DO - 10.1038/s41591-022-01925-w

M3 - Article

SN - 1078-8956

VL - 28

SP - 1797

EP - 1801

JO - Nature Medicine

JF - Nature Medicine

ER -

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

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