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Predicting continuous amyloid PET levels with CSF and plasma brain-derived p-tau217
Lydia Trudel1,2, Joseph Therriault1,2, Arthur C Macedo1,2
1Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Montreal Neurological Institute, Montreal, Quebec, Canada.
Plasma brain-derived phosphorylated tau 217 (BD p-tau217) best reflects the amyloid beta (Aβ) continuum, improving Aβ classification accuracy. This novel biomarker offers enhanced insights into Alzheimer's disease progression.
Area of Science:
- Biomarker discovery and validation
- Neurodegenerative disease research
- Alzheimer's disease diagnostics
Background:
- Accurate staging of amyloid beta (Aβ) burden is crucial for clinical relevance in Alzheimer's disease.
- Conventional phosphorylated tau (p-tau)217 assays identify amyloid positron emission tomography (PET) positivity but have limitations in capturing the full Aβ continuum.
- Brain-derived (BD) p-tau217 assays, enriched for central nervous system tau species, show potential for improved specificity.
Purpose of the Study:
- To evaluate the performance of BD p-tau217 in reflecting the continuous spectrum of Aβ burden.
- To assess the accuracy of BD p-tau217 in classifying participants as Aβ positive or negative across various Centiloid (CL) thresholds.
- To compare the efficacy of conventional and BD p-tau217 assays in both cerebrospinal fluid (CSF) and plasma.
Main Methods:
- Utilized data from 924 participants in the Alzheimer's Disease Neuroimaging Initiative.
- Quantified conventional and BD p-tau217 levels in CSF and plasma using the Alamar NULISAseq panel.
- Correlated biomarker levels with amyloid PET Centiloid values to assess continuous association and classification accuracy.
Main Results:
- Plasma BD p-tau217 exhibited the strongest continuous association with PET CL (R² = 0.63) and the best prediction across the CL spectrum (RMSE = 24.5).
- Prediction accuracy was high in cognitively unimpaired individuals at low CL.
- Reasonable accuracy was observed in cognitively impaired individuals across intermediate-to-high CL thresholds.
Conclusions:
- Plasma BD p-tau217 demonstrates superior performance in capturing the amyloid PET continuum compared to conventional assays.
- BD processing enhances the discriminatory power of p-tau217 in plasma, but not in CSF.
- These findings highlight the potential of plasma BD p-tau217 as a valuable tool for Alzheimer's disease staging.
