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Trajectories of plasma and CSF MTBR-tau243 and phosphorylated-tau species across the Alzheimer's disease continuum

Collij, Lyduine E LU ; Salvadó, Gemma LU ; Horie, Kanta ; Barthélemy, Nicolas R ; Betthauser, Tobey J ; Strandberg, Olof LU ; Smith, Ruben LU ; Palmqvist, Sebastian LU orcid ; Schindler, Suzanne E and Ossenkoppele, Rik LU , et al. (2026) In Nature Communications 17. p.1-13
Abstract

To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models showed that %p-tau217 changes earliest, increasing just before Aβ-PET positivity. Other p-tau species changed later, with smaller dynamic ranges and earlier ceiling effects. %p-tau205 and MTBR-tau243 changes aligned with tau-PET positivity onset,... (More)

To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models showed that %p-tau217 changes earliest, increasing just before Aβ-PET positivity. Other p-tau species changed later, with smaller dynamic ranges and earlier ceiling effects. %p-tau205 and MTBR-tau243 changes aligned with tau-PET positivity onset, while MTBR-tau243-especially plasma eMTBR-tau243-tracked cortical tau burden in later stages. Non-phosphorylated mid-region tau may serve as a late-stage biomarker. Taken together, concurrent assessments of plasma or CSF %p-tau217, %p-tau205, and (e)MTBR-tau243 provides information about different biological events in the disease cascade, which can benefit clinical trials and patient management in clinical practice.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Alzheimer Disease/blood, tau Proteins/blood, Phosphorylation, Biomarkers/blood, Disease Progression, Female, Amyloid beta-Peptides/metabolism, Male, Aged, Positron-Emission Tomography
in
Nature Communications
volume
17
article number
3400
pages
1 - 13
publisher
Nature Publishing Group
external identifiers
  • pmid:41957377
  • scopus:105035471138
ISSN
2041-1723
DOI
10.1038/s41467-026-71732-1
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
94b31a9b-037e-4016-af60-7c6616a9a272
date added to LUP
2026-08-26 11:01:02
date last changed
2026-09-10 04:51:35
@article{94b31a9b-037e-4016-af60-7c6616a9a272,
  abstract     = {{<p>To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models showed that %p-tau217 changes earliest, increasing just before Aβ-PET positivity. Other p-tau species changed later, with smaller dynamic ranges and earlier ceiling effects. %p-tau205 and MTBR-tau243 changes aligned with tau-PET positivity onset, while MTBR-tau243-especially plasma eMTBR-tau243-tracked cortical tau burden in later stages. Non-phosphorylated mid-region tau may serve as a late-stage biomarker. Taken together, concurrent assessments of plasma or CSF %p-tau217, %p-tau205, and (e)MTBR-tau243 provides information about different biological events in the disease cascade, which can benefit clinical trials and patient management in clinical practice.</p>}},
  author       = {{Collij, Lyduine E and Salvadó, Gemma and Horie, Kanta and Barthélemy, Nicolas R and Betthauser, Tobey J and Strandberg, Olof and Smith, Ruben and Palmqvist, Sebastian and Schindler, Suzanne E and Ossenkoppele, Rik and Janelidze, Shorena and Mattsson-Carlgren, Niklas and Bateman, Randall J and Hansson, Oskar}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Alzheimer Disease/blood; tau Proteins/blood; Phosphorylation; Biomarkers/blood; Disease Progression; Female; Amyloid beta-Peptides/metabolism; Male; Aged; Positron-Emission Tomography}},
  language     = {{eng}},
  month        = {{04}},
  pages        = {{1--13}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Trajectories of plasma and CSF MTBR-tau243 and phosphorylated-tau species across the Alzheimer's disease continuum}},
  url          = {{http://dx.doi.org/10.1038/s41467-026-71732-1}},
  doi          = {{10.1038/s41467-026-71732-1}},
  volume       = {{17}},
  year         = {{2026}},
}