Plasma p-tau181/Aβ1-42 ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42 and future cognitive decline

Authors

Christopher J. Fowler
Erik Stoops
Stephanie R. Rainey-Smith, Edith Cowan UniversityFollow
Eugeen Vanmechelen
Jeroen Vanbrabant
Nele Dewit
Kimberley Mauroo
Paul Maruff
Christopher C. Rowe
Jurgen Fripp
Qiao-Xin Li
Pierrick Bourgeat
Steven J. Collins
Ralph N. Martins, Edith Cowan UniversityFollow
Colin L. Masters
James D. Doecke

Document Type

Journal Article

Publication Title

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Volume

14

Issue

1

Publisher

Wiley

School

School of Medical and Health Sciences / Centre of Excellence for Alzheimer's Disease Research and Care

RAS ID

54111

Funders

AIBL and ADx Neurosciences

Comments

Fowler, C. J., Stoops, E., Rainey-Smith, S. R., Vanmeche, E., Vanbrabant, J., Dewit, N., . . . Doecke, J. D. (2022). Plasma p-tau181/Aβ1-42 ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42 and future cognitive decline. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 14(1), article e12375. https://doi.org/10.1002/dad2.12375

Abstract

Background: In Alzheimer's disease (AD), plasma amyloid beta (Aβ)1-42 and phosphorylated tau (p-tau) predict high amyloid status from Aβ positron emission tomography (PET); however, the extent to which combination of these plasma assays can predict remains unknown. Methods: Prototype Simoa assays were used to measure plasma samples from participants who were either cognitively normal (CN) or had mild cognitive impairment (MCI)/AD in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Results: The p-tau181/Aβ1-42 ratio showed the best prediction of Aβ-PET across all participants (area under the curve [AUC] = 0.905, 95% confidence interval [CI]: 0.86–0.95) and in CN (AUC = 0.873; 0.80–0.94), and symptomatic (AUC = 0.908; 0.82–1.00) adults. Plasma p-tau181/Aβ1-42 ratio correlated with cerebrospinal fluid (CSF) p-tau181 (Elecsys, Spearman's ρ = 0.74, P < 0.0001) and predicted abnormal CSF Aβ (AUC = 0.816; 0.74–0.89). The p-tau181/Aβ1-42 ratio also predicted future rates of cognitive decline assessed by AIBL Preclinical Alzheimer Cognitive Composite or Clinical Dementia Rating Sum of Boxes (P < 0.0001). Discussion: Plasma p-tau181/Aβ1-42 ratio predicted both Aβ-PET status and cognitive decline, demonstrating potential as both a diagnostic aid and as a screening and prognostic assay for preclinical AD trials.

DOI

10.1002/dad2.12375

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License