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Prediction of continuous amyloid positron emission tomography with fluid measures of phosphorylated tau and β-amyloid

Mattsson-Carlgren, Niklas LU orcid ; Karlsson, Linda LU orcid ; Tang, Weizhong LU ; Blennow, Kaj LU ; Zetterberg, Henrik LU ; Bateman, Randall J. ; Schindler, Suzanne E. ; Barthelemy, Nicolas ; Palmqvist, Sebastian LU orcid and Stomrud, Erik LU orcid , et al. (2025) In EMBO Molecular Medicine
Abstract

Brain amyloid-β (Aβ) pathology is a core feature of Alzheimer disease (AD) and can be quantified using positron emission tomography (PET). Cerebrospinal fluid (CSF) and plasma biomarkers detect abnormal Aβ, but it is unclear to what degree they can predict quantitative Aβ-PET. We explored plasma and CSF biomarkers in relation to Aβ-PET in the BioFINDER-2 study (N = 1053), and the BioFINDER-1 study (N = 238). We developed a machine learning pipeline to predict Aβ-PET using CSF and plasma measures. The best models achieved R2 = 0.79. Plasma P-tau217 and CSF Aβ42/Aβ40 contributed the most. CSF Aβ42/Aβ40 contributed most to identify Aβ-positivity, while continuous Aβ-PET load within the positive range was best predicted by plasma... (More)

Brain amyloid-β (Aβ) pathology is a core feature of Alzheimer disease (AD) and can be quantified using positron emission tomography (PET). Cerebrospinal fluid (CSF) and plasma biomarkers detect abnormal Aβ, but it is unclear to what degree they can predict quantitative Aβ-PET. We explored plasma and CSF biomarkers in relation to Aβ-PET in the BioFINDER-2 study (N = 1053), and the BioFINDER-1 study (N = 238). We developed a machine learning pipeline to predict Aβ-PET using CSF and plasma measures. The best models achieved R2 = 0.79. Plasma P-tau217 and CSF Aβ42/Aβ40 contributed the most. CSF Aβ42/Aβ40 contributed most to identify Aβ-positivity, while continuous Aβ-PET load within the positive range was best predicted by plasma P-tau217. Models using only plasma measures approached performance of CSF models. Altered metabolism of soluble Aβ may be highly associated with presence of Aβ plaques, while soluble P-tau217 levels may continue to change during build-up of Aβ pathology.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Alzheimer’s Disease, Amyloid, Clinical Trials, PET, Plasma Biomarkers
in
EMBO Molecular Medicine
publisher
Wiley-Blackwell
external identifiers
  • scopus:105023894730
  • pmid:41326715
ISSN
1757-4676
DOI
10.1038/s44321-025-00348-7
language
English
LU publication?
yes
id
b8eceabf-8065-4fc3-9653-11885eb23a60
date added to LUP
2025-12-19 13:11:00
date last changed
2025-12-19 13:11:48
@article{b8eceabf-8065-4fc3-9653-11885eb23a60,
  abstract     = {{<p>Brain amyloid-β (Aβ) pathology is a core feature of Alzheimer disease (AD) and can be quantified using positron emission tomography (PET). Cerebrospinal fluid (CSF) and plasma biomarkers detect abnormal Aβ, but it is unclear to what degree they can predict quantitative Aβ-PET. We explored plasma and CSF biomarkers in relation to Aβ-PET in the BioFINDER-2 study (N = 1053), and the BioFINDER-1 study (N = 238). We developed a machine learning pipeline to predict Aβ-PET using CSF and plasma measures. The best models achieved R<sup>2</sup> = 0.79. Plasma P-tau217 and CSF Aβ42/Aβ40 contributed the most. CSF Aβ42/Aβ40 contributed most to identify Aβ-positivity, while continuous Aβ-PET load within the positive range was best predicted by plasma P-tau217. Models using only plasma measures approached performance of CSF models. Altered metabolism of soluble Aβ may be highly associated with presence of Aβ plaques, while soluble P-tau217 levels may continue to change during build-up of Aβ pathology.</p>}},
  author       = {{Mattsson-Carlgren, Niklas and Karlsson, Linda and Tang, Weizhong and Blennow, Kaj and Zetterberg, Henrik and Bateman, Randall J. and Schindler, Suzanne E. and Barthelemy, Nicolas and Palmqvist, Sebastian and Stomrud, Erik and Janelidze, Shorena and Hansson, Oskar}},
  issn         = {{1757-4676}},
  keywords     = {{Alzheimer’s Disease; Amyloid; Clinical Trials; PET; Plasma Biomarkers}},
  language     = {{eng}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{Prediction of continuous amyloid positron emission tomography with fluid measures of phosphorylated tau and β-amyloid}},
  url          = {{http://dx.doi.org/10.1038/s44321-025-00348-7}},
  doi          = {{10.1038/s44321-025-00348-7}},
  year         = {{2025}},
}