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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.
Background:
Staging amyloid beta (Aβ) burden along a continuous spectrum provides clinically relevant information. Conventional phosphorylated tau (p-tau)217 reliably identifies amyloid positron emission tomography (PET) positivity, but its ability to capture the full Aβ continuum is limited. Recently developed brain-derived (BD) p-tau217 assays enrich for central nervous system tau species and may improve specificity.
Methods:
We tested how closely BD p-tau217 reflected continuous Aβ and how accurately it could classify participants as Aβ positive or negative across different Centiloid (CL) thresholds in 924 participants from the Alzheimer's Disease Neuroimaging Initiative. Conventional and BD cerebrospinal fluid (CSF) and plasma p-tau217 biomarkers were quantified using the Alamar NULISAseq panel.
Results:
Across the full cohort, plasma BD p-tau217 demonstrated the strongest continuous association with PET CL (R2 = 0.63), and the best prediction across the CL spectrum (root mean square error = = 24.5). Prediction was precise in cognitively unimpaired participants at low CL and reasonably accurate in cognitively impaired participants across intermediate-to-high CL.
Conclusions:
Plasma BD p-tau217 best captured the amyloid PET continuum, with BD processing improving discrimination in plasma but not CSF.
