Predictive Value of Plasma Biomarkers in Tau-PET Transitions

Graff-Radford, Jonathan; Syrjanen, Jeremy A.; Vemuri, Prashanthi; Lowe, Val J.; Schwarz, Christopher G.; Wiste, Heather J.; Kremers, Walter K.; Algeciras-Schimnich, Alicia; Pichet Binette, Alexa; Smith, Ruben; Mattsson-Carlgren, Niklas; Palmqvist, Sebastian; Stomrud, Erik; Knopman, David S.; Cogswell, Petrice M.; Petersen, Ronald C.; Hansson, Oskar; Jack, Clifford R.

Predictive Value of Plasma Biomarkers in Tau-PET Transitions

Mark

Graff-Radford, Jonathan ; Syrjanen, Jeremy A. ; Vemuri, Prashanthi ; Lowe, Val J. ; Schwarz, Christopher G. ; Wiste, Heather J. ; Kremers, Walter K. ; Algeciras-Schimnich, Alicia ; Pichet Binette, Alexa ^LU and Smith, Ruben ^LU , et al. (2025) In Annals of Neurology

Abstract: Objective: The objective of this study was to determine the predictive value of amyloid-positron emission tomography (PET) versus the plasma ratio of phosphorylated tau at threonine 217 (p-tau217) to non-phosphorylated tau217 (%p-tau217) for tau-PET transitions (T− to T+). The added value of combining plasma amyloid-β 42 and amyloid-β 40 (Aβ42/40) and %p-tau217 into an amyloid probability score (APS2) was also assessed. Methods: Mayo Clinic Study of Aging (MCSA) participants had plasma markers measured at via mass spectrometry (MS), an amyloid-PET scan, and a tau-PET (meta-temporal region of interest [ROI]) negative scan (standardized uptake value ratio [SUVR] <1.29) at the index (baseline) date, along with one or more follow-up... (More); Objective: The objective of this study was to determine the predictive value of amyloid-positron emission tomography (PET) versus the plasma ratio of phosphorylated tau at threonine 217 (p-tau217) to non-phosphorylated tau217 (%p-tau217) for tau-PET transitions (T− to T+). The added value of combining plasma amyloid-β 42 and amyloid-β 40 (Aβ42/40) and %p-tau217 into an amyloid probability score (APS2) was also assessed. Methods: Mayo Clinic Study of Aging (MCSA) participants had plasma markers measured at via mass spectrometry (MS), an amyloid-PET scan, and a tau-PET (meta-temporal region of interest [ROI]) negative scan (standardized uptake value ratio [SUVR] <1.29) at the index (baseline) date, along with one or more follow-up tau-PET scans. The BioFINDER-2 cohort was used for validation. Cox proportional hazards models adjusted for age, sex, and apolipoprotein (APOE) ε4 were used to assess predictors, with scaling to the interquartile range (IQR) for comparability of hazard ratios (HR). Results: Among 255 tau-PET negative MCSA participants (median age: 71.9 years), 37 converted to tau-PET positive (median follow-up time: 3.81 years). Higher %p-tau217 (HR: 1.52 [95% CI: 1.28–1.80]), amyloid-PET centiloid (HR: 1.47 [95% CI: 1.20–1.79]), and APS2 (HR: 1.62 [95% CI: 1.22–2.16]) predicted tau-PET conversion. However, Aβ42/40 (HR: 0.94 [95% CI: 0.54–1.66]) was not associated with tau-PET conversion. In the BioFINDER-2 cohort (605 tau-negative, median age: 70.2), 33 converted to tau-positive (median follow-up time: 2 years), with higher %p-tau217 (HR: 1.80 [95% CI: 1.50–2.17]), amyloid-PET centiloid (HR: 2.29 [95% CI: 1.77–2.97]), and lower Aβ42/40 (HR: 2.38 [95% CI: 1.17–4.83]) predicting conversion. Interpretation: In two cohorts, %p-tau217 was associated with tau-PET conversion, comparable to amyloid-PET. APS2 also predicted conversion in the MCSA cohort, whereas Aβ42/40 predicted conversion in the BioFINDER-2 cohort, which had more individuals with cognitive impairment. ANN NEUROL 2025.
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Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/4d46dba9-4cf9-4333-b99b-d0551ac29ab0

author

Graff-Radford, Jonathan ; Syrjanen, Jeremy A. ; Vemuri, Prashanthi ; Lowe, Val J. ; Schwarz, Christopher G. ; Wiste, Heather J. ; Kremers, Walter K. ; Algeciras-Schimnich, Alicia ; Pichet Binette, Alexa ^LU and Smith, Ruben ^LU , et al. (More)

Graff-Radford, Jonathan ; Syrjanen, Jeremy A. ; Vemuri, Prashanthi ; Lowe, Val J. ; Schwarz, Christopher G. ; Wiste, Heather J. ; Kremers, Walter K. ; Algeciras-Schimnich, Alicia ; Pichet Binette, Alexa ^LU ; Smith, Ruben ^LU ; Mattsson-Carlgren, Niklas ^LU

; Palmqvist, Sebastian ^LU

; Stomrud, Erik ^LU

; Knopman, David S. ; Cogswell, Petrice M. ; Petersen, Ronald C. ; Hansson, Oskar ^LU

and Jack, Clifford R. (Less)

organization

publishing date

2025

type

Contribution to journal

publication status

epub

subject

Neurology

in

Annals of Neurology

publisher

John Wiley & Sons Inc.

external identifiers

pmid:40927954
scopus:105015561800

ISSN

0364-5134

DOI

10.1002/ana.78003

language

English

LU publication?

yes

id

4d46dba9-4cf9-4333-b99b-d0551ac29ab0

date added to LUP

2025-11-12 15:32:21

date last changed

2025-11-13 03:19:38

@article{4d46dba9-4cf9-4333-b99b-d0551ac29ab0,
  abstract     = {{<p>Objective: The objective of this study was to determine the predictive value of amyloid-positron emission tomography (PET) versus the plasma ratio of phosphorylated tau at threonine 217 (p-tau217) to non-phosphorylated tau217 (%p-tau217) for tau-PET transitions (T− to T+). The added value of combining plasma amyloid-β 42 and amyloid-β 40 (Aβ42/40) and %p-tau217 into an amyloid probability score (APS2) was also assessed. Methods: Mayo Clinic Study of Aging (MCSA) participants had plasma markers measured at via mass spectrometry (MS), an amyloid-PET scan, and a tau-PET (meta-temporal region of interest [ROI]) negative scan (standardized uptake value ratio [SUVR] &lt;1.29) at the index (baseline) date, along with one or more follow-up tau-PET scans. The BioFINDER-2 cohort was used for validation. Cox proportional hazards models adjusted for age, sex, and apolipoprotein (APOE) ε4 were used to assess predictors, with scaling to the interquartile range (IQR) for comparability of hazard ratios (HR). Results: Among 255 tau-PET negative MCSA participants (median age: 71.9 years), 37 converted to tau-PET positive (median follow-up time: 3.81 years). Higher %p-tau217 (HR: 1.52 [95% CI: 1.28–1.80]), amyloid-PET centiloid (HR: 1.47 [95% CI: 1.20–1.79]), and APS2 (HR: 1.62 [95% CI: 1.22–2.16]) predicted tau-PET conversion. However, Aβ42/40 (HR: 0.94 [95% CI: 0.54–1.66]) was not associated with tau-PET conversion. In the BioFINDER-2 cohort (605 tau-negative, median age: 70.2), 33 converted to tau-positive (median follow-up time: 2 years), with higher %p-tau217 (HR: 1.80 [95% CI: 1.50–2.17]), amyloid-PET centiloid (HR: 2.29 [95% CI: 1.77–2.97]), and lower Aβ42/40 (HR: 2.38 [95% CI: 1.17–4.83]) predicting conversion. Interpretation: In two cohorts, %p-tau217 was associated with tau-PET conversion, comparable to amyloid-PET. APS2 also predicted conversion in the MCSA cohort, whereas Aβ42/40 predicted conversion in the BioFINDER-2 cohort, which had more individuals with cognitive impairment. ANN NEUROL 2025.</p>}},
  author       = {{Graff-Radford, Jonathan and Syrjanen, Jeremy A. and Vemuri, Prashanthi and Lowe, Val J. and Schwarz, Christopher G. and Wiste, Heather J. and Kremers, Walter K. and Algeciras-Schimnich, Alicia and Pichet Binette, Alexa and Smith, Ruben and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Stomrud, Erik and Knopman, David S. and Cogswell, Petrice M. and Petersen, Ronald C. and Hansson, Oskar and Jack, Clifford R.}},
  issn         = {{0364-5134}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Annals of Neurology}},
  title        = {{Predictive Value of Plasma Biomarkers in Tau-PET Transitions}},
  url          = {{http://dx.doi.org/10.1002/ana.78003}},
  doi          = {{10.1002/ana.78003}},
  year         = {{2025}},
}

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Predictive Value of Plasma Biomarkers in Tau-PET Transitions