The potential of key Alzheimer's plasma biomarkers to mimic tau PET MUBADA-based disease staging.
Plasma P-tau217 accurately distinguishes amyloid-negative from amyloid-positive Alzheimer's patients.
The potential of key Alzheimer's plasma biomarkers to mimic tau PET MUBADA-based disease staging.
Staging tau burden with plasma biomarkers would offer a scalable alternative to staging with tau-PET.
This study investigated whether key plasma biomarkers P-tau217, P-tau181, Aβ42/40, GFAP and NfL can be used to accurately stage amyloid status (A-/A+) and tau-PET burden, and evaluated the relation of such a plasma-based staging system with cognitive outcomes over time.
We included 105 participants with subjective cognitive decline (n = 27 A-, n = 18 A+), A+ mild cognitive impairment (n = 10) or A + AD-dementia (n = 50) from the Amsterdam Dementia Cohort who underwent [ 18 F]flortaucipir PET-burden assessment (T low , T intermediate or T high ; based on MUBADA SUVr) and longitudinal cognitive assessment (average follow-up: 4.1 ± 3.5 years).
higher scores mean better separation of amyloid negative from positive
27 participants were A-T PET_low , 22 A+T PET_low , 27 A+T PET_int and 29 A+T PET_high .
To discriminate A+T PET_high participants from A+T PET_low/int participants, also P-tau217 performed best among all markers (AUC = 0.74 [95% CI: 0.618-0.862]).
A combination of Wald's backward-selected plasma markers did not statistically improve discriminative performance (DeLong's p > 0.05; two-marker combinations selected).
Applying two cutoffs for P-tau217 as well as for the two-marker combinations, at 90% specificity to discriminate subsequent groups, we derived two plasma-based staging schemes.
Performance of plasma-based staging approaches developed in this study were high when discriminating individuals without amyloid pathology, while this was moderate when discriminating amyloid positive individuals with a high tau-PET burden.
Our linear mixed models findings visualize that tau staging in amyloid-positive individuals remains optimally performed with tau-PET scans.