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. 2023 Mar;64(3):437-443.
doi: 10.2967/jnumed.122.264279. Epub 2022 Oct 13.

A Head-to-Head Comparison Between Plasma pTau181 and Tau PET Along the Alzheimer's Disease Continuum

Emma M Coomans  1 , Inge M W Verberk  2 , Rik Ossenkoppele  3   4 , Sander C J Verfaillie  5   6 , Denise Visser  5 , Mariam Gouda  2 , Hayel Tuncel  5 , Emma E Wolters  5 , Tessa Timmers  5 , Albert D Windhorst  5 , Sandeep S V Golla  5 , Philip Scheltens  3 , Wiesje M van, der Flier  3   7 , Bart N M van Berckel  5 , Charlotte E Teunissen  2
Affiliations

A Head-to-Head Comparison Between Plasma pTau181 and Tau PET Along the Alzheimer's Disease Continuum

Emma M Coomans et al. J Nucl Med. 2023 Mar.

Abstract

Both plasma tau phosphorylated at threonine-181 (pTau181) and tau PET show potential for detecting Alzheimer's disease (AD) pathology and predicting clinical progression. In this study, we performed a head-to-head comparison between plasma pTau181 and tau PET along the AD continuum. Methods: We included participants from the Amsterdam Dementia Cohort who underwent 18F-flortaucipir (tau) PET and had a plasma sample biobanked within 12 mo from tau PET. Fifty subjective cognitive decline (SCD) participants (31 Aβ-negative and 19 Aβ-positive) and 60 Aβ-positive participants with mild cognitive impairment (MCI) or dementia due to AD were included. A subset had 2-y longitudinal plasma pTau181 and tau PET available (n = 40). Longitudinal neuropsychological test data covering 3.2 ± 2.7 y from both before and after tau PET were available. Plasma pTau181 and tau PET were compared in their accuracies in discriminating between cognitive stage (MCI/AD vs. SCD) and preclinical Aβ status (SCD Aβ-positive vs. SCD Aβ-negative), their associations with cross-sectional and longitudinal neuropsychological test performance, and their longitudinal changes over time. Results: When discriminating between preclinical Aβ status, the area under the curve (AUC) for plasma pTau181 (0.83) and tau PET (entorhinal, 0.87; temporal, 0.85; neocortical, 0.67) were equally high (all DeLong P > 0.05), but tau PET outperformed plasma pTau181 in discriminating MCI/AD from SCD (AUC for plasma pTau181: 0.74; AUCs for tau PET: entorhinal, 0.89; temporal, 0.92; neocortical, 0.89) (all P < 0.01). Overall, tau PET showed stronger associations with cognitive decline and was associated with a wider variety of cognitive tests than plasma pTau181 (plasma pTau181, -0.02 > β < -0.12; tau PET, -0.01 > β < -0.22). Both plasma pTau181 and tau PET increased more steeply over time in MCI/AD than in SCD (P < 0.05), but only tau PET annual changes were associated with cognitive decline. Conclusion: Our results suggest that plasma pTau181 and tau PET perform equally well in identifying Aβ pathology but that tau PET better monitors disease stage and clinical progression.

Keywords: Alzheimer’s disease; plasma pTau181; tau PET.

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Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
Associations between plasma pTau181 and tau PET in SCD and MCI/AD (A) and SCD Aβ-negative and SCD Aβ-positive (B) participants. *P < 0.5. **P < 0.01. ***P < 0.001.
FIGURE 2.
FIGURE 2.
(A and C) Plasma pTau181 and tau PET BPND stratified for SCD and MCI/AD (A) and for SCD Aβ-negative and SCD Aβ-positive MCI due to AD and AD dementia (C). (B and D) AUCs for discriminating SCD from MCI/AD (B) and SCD Aβ-negative from SCD Aβ-positive (D) participants. *P < 0.5. **P < 0.01. ***P < 0.001.
FIGURE 3.
FIGURE 3.
Heat plots reflecting standardized β-estimates (color scale) and significance levels from LMMs between plasma pTau181 or tau PET (predictor) and cross-sectional (A) and longitudinal (B) cognitive performance (outcome variables) (age-, sex-, and education-adjusted). *Uncorrected P < 0.05. **FDR P < 0.05. TMT-B = trail-making test B.
FIGURE 4.
FIGURE 4.
Spaghetti plots of scaled longitudinal plasma pTau181 and tau PET in SCD and MCI/AD.
See this image and copyright information in PMC

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