TY - JOUR
T1 - A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings
AU - Brum, Wagner S.
AU - Cullen, Nicholas C.
AU - Therriault, Joseph
AU - Janelidze, Shorena
AU - Rahmouni, Nesrine
AU - Stevenson, Jenna
AU - Servaes, Stijn
AU - Benedet, Andrea L.
AU - Zimmer, Eduardo R.
AU - Stomrud, Erik
AU - Palmqvist, Sebastian
AU - Zetterberg, Henrik
AU - Frisoni, Giovanni B.
AU - Ashton, Nicholas J.
AU - Blennow, Kaj
AU - Mattsson-Carlgren, Niklas
AU - Rosa-Neto, Pedro
AU - Hansson, Oskar
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-46603-2
DO - 10.1038/s41467-024-46603-2
M3 - Article
C2 - 38486040
AN - SCOPUS:85187899626
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2311
ER -