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.
Keywords
Alzheimer's disease, amyloid beta amyloid imaging, blood biomarkers, blood diagnostic for Alzheimer's disease, cerebrospinal fluid, phosphorylated tau, plasma amyloid beta, plasma phosphorylated tau181, positron emission tomography
Document Type
Journal Article
Date of Publication
1-1-2022
Volume
14
Issue
1
Publication Title
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
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
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
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