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Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals
Different tau biomarkers become abnormal at different stages of Alzheimer’s disease, with CSF phospho-tau typically becoming elevated at subthreshold levels of tau-PET binding. To capitalize on the temporal order of tau biomarker-abnormality and capture the earliest changes of tau accumulation, we i...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115173/ https://www.ncbi.nlm.nih.gov/pubmed/36084009 http://dx.doi.org/10.1093/brain/awac329 |
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author | Groot, Colin Smith, Ruben Stomrud, Erik Binette, Alexa Pichet Leuzy, Antoine Wuestefeld, Anika Wisse, Laura E M Palmqvist, Sebastian Mattsson-Carlgren, Niklas Janelidze, Shorena Strandberg, Olof Ossenkoppele, Rik Hansson, Oskar |
author_facet | Groot, Colin Smith, Ruben Stomrud, Erik Binette, Alexa Pichet Leuzy, Antoine Wuestefeld, Anika Wisse, Laura E M Palmqvist, Sebastian Mattsson-Carlgren, Niklas Janelidze, Shorena Strandberg, Olof Ossenkoppele, Rik Hansson, Oskar |
author_sort | Groot, Colin |
collection | PubMed |
description | Different tau biomarkers become abnormal at different stages of Alzheimer’s disease, with CSF phospho-tau typically becoming elevated at subthreshold levels of tau-PET binding. To capitalize on the temporal order of tau biomarker-abnormality and capture the earliest changes of tau accumulation, we implemented an observational study design to examine longitudinal changes in tau-PET, cortical thickness and cognitive decline in amyloid-β-positive individuals with elevated CSF p-tau levels (P+) but subthreshold Tau-PET retention (T−). To this end, individuals without dementia (i.e. cognitively unimpaired or mild cognitive impairment, n = 231) were selected from the BioFINDER-2 study. Amyloid-β-positive (A+) individuals were categorized into biomarker groups based on cut-offs for abnormal CSF p-tau(217) and (18)F-RO948 (Tau) PET, yielding groups of tau-concordant-negative (A+P−T−; n = 30), tau-discordant (i.e. A+P+T−; n = 48) and tau-concordant-positive (A+P+T+; n = 18) individuals. In addition, 135 amyloid-β-negative, tau-negative, cognitively unimpaired individuals served as controls. Differences in annual change in regional tau-PET, cortical thickness and cognition between the groups were assessed using general linear models, adjusted for age, sex, clinical diagnosis and (for cognitive measures only) education. Mean follow-up time was ∼2 years. Longitudinal increase in tau-PET was faster in the A+P+T− group than in the control and A+P−T− groups across medial temporal and neocortical regions, with the highest accumulation rates in the medial temporal lobe. The A+P+T− group showed a slower rate of increase in tau-PET compared to the A+P+T+ group, primarily in neocortical regions. We did not detect differences in yearly change in cortical thickness or in cognitive decline between the A+P+T− and A+P−T− groups. The A+P+T+ group, however, showed faster cognitive decline compared to all other groups. Altogether, these findings suggest that the A+P+T− biomarker profile in persons without dementia is associated with an isolated effect on increased tau-PET accumulation rates but not on cortical thinning and cognitive decline. While this suggests that the tau-discordant biomarker profile is not strongly associated with short-term clinical decline, this group does represent an interesting population for monitoring the effects of interventions with disease-modifying agents on tau accumulation in early Alzheimer’s disease, and for examining the emergence of tau aggregates in Alzheimer’s disease. Further, we suggest updating the AT(N) criteria for Alzheimer’s disease biomarker classification to APT(N). |
format | Online Article Text |
id | pubmed-10115173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101151732023-04-20 Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals Groot, Colin Smith, Ruben Stomrud, Erik Binette, Alexa Pichet Leuzy, Antoine Wuestefeld, Anika Wisse, Laura E M Palmqvist, Sebastian Mattsson-Carlgren, Niklas Janelidze, Shorena Strandberg, Olof Ossenkoppele, Rik Hansson, Oskar Brain Original Article Different tau biomarkers become abnormal at different stages of Alzheimer’s disease, with CSF phospho-tau typically becoming elevated at subthreshold levels of tau-PET binding. To capitalize on the temporal order of tau biomarker-abnormality and capture the earliest changes of tau accumulation, we implemented an observational study design to examine longitudinal changes in tau-PET, cortical thickness and cognitive decline in amyloid-β-positive individuals with elevated CSF p-tau levels (P+) but subthreshold Tau-PET retention (T−). To this end, individuals without dementia (i.e. cognitively unimpaired or mild cognitive impairment, n = 231) were selected from the BioFINDER-2 study. Amyloid-β-positive (A+) individuals were categorized into biomarker groups based on cut-offs for abnormal CSF p-tau(217) and (18)F-RO948 (Tau) PET, yielding groups of tau-concordant-negative (A+P−T−; n = 30), tau-discordant (i.e. A+P+T−; n = 48) and tau-concordant-positive (A+P+T+; n = 18) individuals. In addition, 135 amyloid-β-negative, tau-negative, cognitively unimpaired individuals served as controls. Differences in annual change in regional tau-PET, cortical thickness and cognition between the groups were assessed using general linear models, adjusted for age, sex, clinical diagnosis and (for cognitive measures only) education. Mean follow-up time was ∼2 years. Longitudinal increase in tau-PET was faster in the A+P+T− group than in the control and A+P−T− groups across medial temporal and neocortical regions, with the highest accumulation rates in the medial temporal lobe. The A+P+T− group showed a slower rate of increase in tau-PET compared to the A+P+T+ group, primarily in neocortical regions. We did not detect differences in yearly change in cortical thickness or in cognitive decline between the A+P+T− and A+P−T− groups. The A+P+T+ group, however, showed faster cognitive decline compared to all other groups. Altogether, these findings suggest that the A+P+T− biomarker profile in persons without dementia is associated with an isolated effect on increased tau-PET accumulation rates but not on cortical thinning and cognitive decline. While this suggests that the tau-discordant biomarker profile is not strongly associated with short-term clinical decline, this group does represent an interesting population for monitoring the effects of interventions with disease-modifying agents on tau accumulation in early Alzheimer’s disease, and for examining the emergence of tau aggregates in Alzheimer’s disease. Further, we suggest updating the AT(N) criteria for Alzheimer’s disease biomarker classification to APT(N). Oxford University Press 2022-09-09 /pmc/articles/PMC10115173/ /pubmed/36084009 http://dx.doi.org/10.1093/brain/awac329 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Groot, Colin Smith, Ruben Stomrud, Erik Binette, Alexa Pichet Leuzy, Antoine Wuestefeld, Anika Wisse, Laura E M Palmqvist, Sebastian Mattsson-Carlgren, Niklas Janelidze, Shorena Strandberg, Olof Ossenkoppele, Rik Hansson, Oskar Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals |
title | Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals |
title_full | Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals |
title_fullStr | Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals |
title_full_unstemmed | Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals |
title_short | Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals |
title_sort | phospho-tau with subthreshold tau-pet predicts increased tau accumulation rates in amyloid-positive individuals |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115173/ https://www.ncbi.nlm.nih.gov/pubmed/36084009 http://dx.doi.org/10.1093/brain/awac329 |
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