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Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects

Pereira, Joana B. LU ; Janelidze, Shorena LU ; Stomrud, Erik LU orcid ; Palmqvist, Sebastian LU orcid ; Van Westen, Danielle LU orcid ; Dage, Jeffrey L. ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2021) In Brain 144(9). p.2826-2836
Abstract

It is currently unclear whether plasma biomarkers can be used as independent prognostic tools to predict changes associated with early Alzheimer's disease. In this study, we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non-demented individuals. To achieve this, plasma amyloid-β 42/40 (Aβ42/40), phosphorylated-tau181, phosphorylated-tau217 and neurofilament light were determined in 159 non-demented individuals, 123 patients with Alzheimer's disease dementia and 35 patients with a non-Alzheimer's dementia from the Swedish BioFINDER-2 study, who underwent longitudinal amyloid (18F-flutemetamol) and tau (18F-RO948) PET, structural... (More)

It is currently unclear whether plasma biomarkers can be used as independent prognostic tools to predict changes associated with early Alzheimer's disease. In this study, we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non-demented individuals. To achieve this, plasma amyloid-β 42/40 (Aβ42/40), phosphorylated-tau181, phosphorylated-tau217 and neurofilament light were determined in 159 non-demented individuals, 123 patients with Alzheimer's disease dementia and 35 patients with a non-Alzheimer's dementia from the Swedish BioFINDER-2 study, who underwent longitudinal amyloid (18F-flutemetamol) and tau (18F-RO948) PET, structural MRI (T1-weighted) and cognitive testing. Our univariate linear mixed effect models showed there were several significant associations between the plasma biomarkers with imaging and cognitive measures. However, when all biomarkers were included in the same multivariate linear mixed effect models, we found that increased longitudinal amyloid-PET signals were independently predicted by low baseline plasma Aβ42/40 (P = 0.012), whereas increased tau-PET signals, brain atrophy and worse cognition were independently predicted by high plasma phosphorylated-tau217 (P < 0.004). These biomarkers performed equally well or better than the corresponding biomarkers measured in the CSF. In addition, they showed a similar performance to binary plasma biomarker values defined using the Youden index, which can be more easily implemented in the clinic. In addition, plasma Aβ42/40 and phosphorylated-tau217 did not predict longitudinal changes in patients with a non-Alzheimer's neurodegenerative disorder. In conclusion, our findings indicate that plasma Aβ42/40 and phosphorylated-tau217 could be useful in clinical practice, research and drug development as prognostic markers of future Alzheimer's disease pathology.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amyloid-β, cognition, MRI, PET, plasma biomarkers, tau PET
in
Brain
volume
144
issue
9
pages
11 pages
publisher
Oxford University Press
external identifiers
  • scopus:85119341551
  • pmid:34077494
ISSN
0006-8950
DOI
10.1093/brain/awab163
language
English
LU publication?
yes
id
eda086fe-fea0-4abb-aee9-762a379ed053
date added to LUP
2021-12-03 11:01:43
date last changed
2024-06-15 22:01:53
@article{eda086fe-fea0-4abb-aee9-762a379ed053,
  abstract     = {{<p>It is currently unclear whether plasma biomarkers can be used as independent prognostic tools to predict changes associated with early Alzheimer's disease. In this study, we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non-demented individuals. To achieve this, plasma amyloid-β 42/40 (Aβ42/40), phosphorylated-tau181, phosphorylated-tau217 and neurofilament light were determined in 159 non-demented individuals, 123 patients with Alzheimer's disease dementia and 35 patients with a non-Alzheimer's dementia from the Swedish BioFINDER-2 study, who underwent longitudinal amyloid (18F-flutemetamol) and tau (18F-RO948) PET, structural MRI (T1-weighted) and cognitive testing. Our univariate linear mixed effect models showed there were several significant associations between the plasma biomarkers with imaging and cognitive measures. However, when all biomarkers were included in the same multivariate linear mixed effect models, we found that increased longitudinal amyloid-PET signals were independently predicted by low baseline plasma Aβ42/40 (P = 0.012), whereas increased tau-PET signals, brain atrophy and worse cognition were independently predicted by high plasma phosphorylated-tau217 (P &lt; 0.004). These biomarkers performed equally well or better than the corresponding biomarkers measured in the CSF. In addition, they showed a similar performance to binary plasma biomarker values defined using the Youden index, which can be more easily implemented in the clinic. In addition, plasma Aβ42/40 and phosphorylated-tau217 did not predict longitudinal changes in patients with a non-Alzheimer's neurodegenerative disorder. In conclusion, our findings indicate that plasma Aβ42/40 and phosphorylated-tau217 could be useful in clinical practice, research and drug development as prognostic markers of future Alzheimer's disease pathology.</p>}},
  author       = {{Pereira, Joana B. and Janelidze, Shorena and Stomrud, Erik and Palmqvist, Sebastian and Van Westen, Danielle and Dage, Jeffrey L. and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  issn         = {{0006-8950}},
  keywords     = {{amyloid-β; cognition; MRI; PET; plasma biomarkers; tau PET}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{2826--2836}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects}},
  url          = {{http://dx.doi.org/10.1093/brain/awab163}},
  doi          = {{10.1093/brain/awab163}},
  volume       = {{144}},
  year         = {{2021}},
}