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A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings

Brum, Wagner S. ; Cullen, Nicholas C. LU ; Therriault, Joseph ; Janelidze, Shorena LU ; Rahmouni, Nesrine ; Stevenson, Jenna ; Servaes, Stijn ; Benedet, Andrea L. ; Zimmer, Eduardo R. and Stomrud, Erik LU orcid , et al. (2024) In Nature Communications 15(1).
Abstract

Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; “saved scans”) and the tau-PET-positivity rate among participants above the cutoffs (who would undergo... (More)

Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; “saved scans”) and the tau-PET-positivity rate among participants above the cutoffs (who would undergo tau-PET; “positive predictive value”). Generally, plasma pTau217 performed best. At the 95% sensitivity cutoff in both cohorts, pTau217 resulted in avoiding nearly half tau-PET scans, with a tau-PET-positivity rate among those who would be referred for a scan around 70%. And although tau-PET was strongly associated with subsequent cognitive decline, in BioFINDER-2 it predicted cognitive decline only among individuals above the referral cutoff on plasma pTau217, supporting that this workflow could reduce prognostically uninformative tau-PET scans. In conclusion, plasma pTau217 may guide selection of patients for tau-PET, when accurate prognostic information is of clinical value.

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type
Contribution to journal
publication status
published
subject
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Nature Communications
volume
15
issue
1
article number
2311
publisher
Nature Publishing Group
external identifiers
  • pmid:38486040
  • scopus:85187899626
ISSN
2041-1723
DOI
10.1038/s41467-024-46603-2
language
English
LU publication?
yes
id
5d43c4dc-e6f2-4db8-8969-e972c0c75a7b
date added to LUP
2024-04-04 13:27:57
date last changed
2024-04-18 15:43:35
@article{5d43c4dc-e6f2-4db8-8969-e972c0c75a7b,
  abstract     = {{<p>Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; “saved scans”) and the tau-PET-positivity rate among participants above the cutoffs (who would undergo tau-PET; “positive predictive value”). Generally, plasma pTau217 performed best. At the 95% sensitivity cutoff in both cohorts, pTau217 resulted in avoiding nearly half tau-PET scans, with a tau-PET-positivity rate among those who would be referred for a scan around 70%. And although tau-PET was strongly associated with subsequent cognitive decline, in BioFINDER-2 it predicted cognitive decline only among individuals above the referral cutoff on plasma pTau217, supporting that this workflow could reduce prognostically uninformative tau-PET scans. In conclusion, plasma pTau217 may guide selection of patients for tau-PET, when accurate prognostic information is of clinical value.</p>}},
  author       = {{Brum, Wagner S. and Cullen, Nicholas C. and Therriault, Joseph and Janelidze, Shorena and Rahmouni, Nesrine and Stevenson, Jenna and Servaes, Stijn and Benedet, Andrea L. and Zimmer, Eduardo R. and Stomrud, Erik and Palmqvist, Sebastian and Zetterberg, Henrik and Frisoni, Giovanni B. and Ashton, Nicholas J. and Blennow, Kaj and Mattsson-Carlgren, Niklas and Rosa-Neto, Pedro and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-46603-2}},
  doi          = {{10.1038/s41467-024-46603-2}},
  volume       = {{15}},
  year         = {{2024}},
}