The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

for the AddNeuroMed consortium

doi:10.1002/alz.12283

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

for the AddNeuroMed consortium

Research output: Contribution to journal › Article › peer-review

225 Citations (Scopus)

Abstract

Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.

Original language	English
Pages (from-to)	1145-1156
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	17
Issue number	7
DOIs	https://doi.org/10.1002/alz.12283
Publication status	Published - Jul 2021

Keywords

Alzheimer's disease
magnetic resonance imaging
phosphorylated tau
plasma biomarkers

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10.1002/alz.12283

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@article{c3585227895f4b06a146e25ac8df2b22,

title = "The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease",

abstract = "Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.",

keywords = "Alzheimer's disease, magnetic resonance imaging, phosphorylated tau, plasma biomarkers",

author = "{for the AddNeuroMed consortium} and Joel Simr{\'e}n and Antoine Leuzy and Karikari, {Thomas K.} and Abdul Hye and Benedet, {Andr{\'e}a Lessa} and Juan Lantero-Rodriguez and Niklas Mattsson-Carlgren and Michael Sch{\"o}ll and Patrizia Mecocci and Bruno Vellas and Magda Tsolaki and Iwona Kloszewska and Hilkka Soininen and Simon Lovestone and Dag Aarsland and Oskar Hansson and Pedro Rosa-Neto and Eric Westman and Kaj Blennow and Henrik Zetterberg and Ashton, {Nicholas J.}",

note = "Funding Information: Anna Lisa and Brother Bj{\"o}rnsson's Foundation. Dr. Kaj Blennow is supported by the Swedish Research Council (#2017‐00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB‐201809‐2016615), the Swedish Alzheimer Foundation (#AF‐742881), Hj{\"a}rnfonden, Sweden (#FO2017‐0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF‐agreement (#ALFGBG‐715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019‐466‐236). Dr. Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018‐02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG‐720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809‐2016862), and the UK Dementia Research Institute at UCL. Funding Information: Anna Lisa and Brother Bj?rnsson's Foundation. Dr. Kaj Blennow is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hj?rnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). Dr. Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jul,

doi = "10.1002/alz.12283",

language = "English",

volume = "17",

pages = "1145--1156",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

number = "7",

}

TY - JOUR

T1 - The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

AU - for the AddNeuroMed consortium

AU - Simrén, Joel

AU - Leuzy, Antoine

AU - Karikari, Thomas K.

AU - Hye, Abdul

AU - Benedet, Andréa Lessa

AU - Lantero-Rodriguez, Juan

AU - Mattsson-Carlgren, Niklas

AU - Schöll, Michael

AU - Mecocci, Patrizia

AU - Vellas, Bruno

AU - Tsolaki, Magda

AU - Kloszewska, Iwona

AU - Soininen, Hilkka

AU - Lovestone, Simon

AU - Aarsland, Dag

AU - Hansson, Oskar

AU - Rosa-Neto, Pedro

AU - Westman, Eric

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Ashton, Nicholas J.

N1 - Funding Information: Anna Lisa and Brother Björnsson's Foundation. Dr. Kaj Blennow is supported by the Swedish Research Council (#2017‐00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB‐201809‐2016615), the Swedish Alzheimer Foundation (#AF‐742881), Hjärnfonden, Sweden (#FO2017‐0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF‐agreement (#ALFGBG‐715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019‐466‐236). Dr. Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018‐02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG‐720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809‐2016862), and the UK Dementia Research Institute at UCL. Funding Information: Anna Lisa and Brother Bj?rnsson's Foundation. Dr. Kaj Blennow is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hj?rnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). Dr. Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. Publisher Copyright: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.

AB - Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.

KW - Alzheimer's disease

KW - magnetic resonance imaging

KW - phosphorylated tau

KW - plasma biomarkers

UR - http://www.scopus.com/inward/record.url?scp=85099864986&partnerID=8YFLogxK

U2 - 10.1002/alz.12283

DO - 10.1002/alz.12283

M3 - Article

AN - SCOPUS:85099864986

SN - 1552-5260

VL - 17

SP - 1145

EP - 1156

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 7

ER -

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

Abstract

Keywords

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