Abstract
Original language | English |
---|---|
Article number | e14398 |
Journal | EMBO molecular medicine |
Volume | 13 |
Issue number | 8 |
DOIs | |
Publication status | Published - 9 Aug 2021 |
Keywords
- Alzheimer's disease
- CSF
- PET
- plasma
- tau
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In: EMBO molecular medicine, Vol. 13, No. 8, e14398, 09.08.2021.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Tau PET correlates with different Alzheimer’s disease-related features compared to CSF and plasma p-tau biomarkers
AU - Ossenkoppele, Rik
AU - Reimand, Juhan
AU - Smith, Ruben
AU - Leuzy, Antoine
AU - Strandberg, Olof
AU - Palmqvist, Sebastian
AU - Stomrud, Erik
AU - Zetterberg, Henrik
AU - Scheltens, Philip
AU - Dage, Jeffrey L.
AU - Bouwman, Femke
AU - Blennow, Kaj
AU - The Alzheimer's Disease Neuroimaging Initiative
AU - Mattsson-Carlgren, Niklas
AU - Janelidze, Shorena
AU - Hansson, Oskar
N1 - Funding Information: This project has received funding from the European Research Council (949570), the Swedish Research Council (2016-00906), the Knut and Alice Wallenberg foundation (2017-0383), the Marianne and Marcus Wallenberg foundation (2015.0125), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation (AF-939932), the Swedish Brain Foundation (FO2019-0326), The Parkinson foundation of Sweden (1280/20), the Sk?ne University Hospital Foundation (2020-O000028), Regionalt Forskningsst?d (2020-0314) and the Swedish federal government under the ALF agreement (2018-Projekt0279). The precursor of 18F-flutemetamol was provided by GE Healthcare in BioFINDER-2 and the precursor of 18F-RO948 was provided by Roche in BioFINDER-2. HZ is a Wallenberg Scholar. KB is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hj?rnfonden, Sweden (#FO2017-0243) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: This project has received funding from the European Research Council (949570), the Swedish Research Council (2016‐00906), the Knut and Alice Wallenberg foundation (2017‐0383), the Marianne and Marcus Wallenberg foundation (2015.0125), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation (AF‐939932), the Swedish Brain Foundation (FO2019‐0326), The Parkinson foundation of Sweden (1280/20), the Skåne University Hospital Foundation (2020‐O000028), Regionalt Forskningsstöd (2020‐0314) and the Swedish federal government under the ALF agreement (2018‐Projekt0279). The precursor of F‐flutemetamol was provided by GE Healthcare in BioFINDER‐2 and the precursor of F‐RO948 was provided by Roche in BioFINDER‐2. HZ is a Wallenberg Scholar. KB is supported by the Swedish Research Council (#2017‐00915), the Swedish Alzheimer Foundation (#AF‐742881), Hjärnfonden, Sweden (#FO2017‐0243) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF‐agreement (#ALFGBG‐715986). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. 18 18 Publisher Copyright: © 2021 The Authors. Published under the terms of the CC BY 4.0 license Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/9
Y1 - 2021/8/9
N2 - PET, CSF and plasma biomarkers of tau pathology may be differentially associated with Alzheimer's disease (AD)-related demographic, cognitive, genetic and neuroimaging markers. We examined 771 participants with normal cognition, mild cognitive impairment or dementia from BioFINDER-2 (n = 400) and ADNI (n = 371). All had tau-PET ([18F]RO948 in BioFINDER-2, [18F]flortaucipir in ADNI) and CSF p-tau181 biomarkers available. Plasma p-tau181 and plasma/CSF p-tau217 were available in BioFINDER-2 only. Concordance between PET, CSF and plasma tau biomarkers ranged between 66 and 95%. Across the whole group, ridge regression models showed that increased CSF and plasma p-tau181 and p-tau217 levels were independently of tau PET associated with higher age, and APOEɛ4-carriership and Aβ-positivity, while increased tau-PET signal in the temporal cortex was associated with worse cognitive performance and reduced cortical thickness. We conclude that biofluid and neuroimaging markers of tau pathology convey partly independent information, with CSF and plasma p-tau181 and p-tau217 levels being more tightly linked with early markers of AD (especially Aβ-pathology), while tau-PET shows the strongest associations with cognitive and neurodegenerative markers of disease progression.
AB - PET, CSF and plasma biomarkers of tau pathology may be differentially associated with Alzheimer's disease (AD)-related demographic, cognitive, genetic and neuroimaging markers. We examined 771 participants with normal cognition, mild cognitive impairment or dementia from BioFINDER-2 (n = 400) and ADNI (n = 371). All had tau-PET ([18F]RO948 in BioFINDER-2, [18F]flortaucipir in ADNI) and CSF p-tau181 biomarkers available. Plasma p-tau181 and plasma/CSF p-tau217 were available in BioFINDER-2 only. Concordance between PET, CSF and plasma tau biomarkers ranged between 66 and 95%. Across the whole group, ridge regression models showed that increased CSF and plasma p-tau181 and p-tau217 levels were independently of tau PET associated with higher age, and APOEɛ4-carriership and Aβ-positivity, while increased tau-PET signal in the temporal cortex was associated with worse cognitive performance and reduced cortical thickness. We conclude that biofluid and neuroimaging markers of tau pathology convey partly independent information, with CSF and plasma p-tau181 and p-tau217 levels being more tightly linked with early markers of AD (especially Aβ-pathology), while tau-PET shows the strongest associations with cognitive and neurodegenerative markers of disease progression.
KW - Alzheimer's disease
KW - CSF
KW - PET
KW - plasma
KW - tau
UR - http://www.scopus.com/inward/record.url?scp=85111722211&partnerID=8YFLogxK
U2 - https://doi.org/10.15252/emmm.202114398
DO - https://doi.org/10.15252/emmm.202114398
M3 - Article
C2 - 34254442
SN - 1757-4676
VL - 13
JO - EMBO molecular medicine
JF - EMBO molecular medicine
IS - 8
M1 - e14398
ER -