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

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 accumulat...

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Published in:Brain (London, England : 1878) Vol. 144; no. 9; p. 2826
Main Authors: Pereira, Joana B, Janelidze, Shorena, Stomrud, Erik, Palmqvist, Sebastian, van Westen, Danielle, Dage, Jeffrey L, Mattsson-Carlgren, Niklas, Hansson, Oskar
Format: Journal Article
Language:English
Published: England 22.10.2021
Subjects:
Adaptor Proteins, Signal Transducing - blood
Adult
Aged
Aged, 80 and over
Amyloid beta-Peptides - blood
Atrophy - blood
Biomarkers - blood
Brain - diagnostic imaging
Brain - metabolism
Cohort Studies
Female
Humans
Longitudinal Studies
Male
Middle Aged
Neuropsychological Tests
Peptide Fragments - blood
Predictive Value of Tests
amyloid-β
plasma biomarkers
cognition
MRI
PET
tau PET
ISSN:1460-2156, 1460-2156
Online Access:Get more information
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Summary: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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ISSN:1460-2156
1460-2156
DOI:10.1093/brain/awab163