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HEAD-TO-HEAD COMPARISON OF PLASMA BIOMARKERS OF AMYLOID, TAU, AND INFLAMMATION FOR THE IDENTIFICATION OF AD PATHOPHYSIOLOGY
Abstract
Aims
To perform a head-to-head comparison of plasma phosphorylated tau (p-Tau) 181 and p-Tau231, neurofilament light chain (NfL), glial fibrillary protein (GFAP), and amyloid (Aβ)42/Aβ40 against Aβ PET and Tau PET across the Alzheimer Disease (AD) spectrum.
Methods
Plasma p-Tau231, p-Tau181, NfL, GFAP, Aβ42/Aβ40 were measured by Simoa, [18F]AZD4694 Aβ-PET, [18F]MK6240 Tau-PET, MRI and cognitive assessment from 230 individuals [142 Cognitive unimpaired (CU), 88 cognitive impaired (CI)] were obtained from the McGill TRIAD cohort. Linear regressions test the associations between biomarkers. Demographics (sex, age, and APOE ε4 status) were added to the models when appropriated. The discriminative performance of biomarkers was assessed with the area under the curve (AUC).
Results
In the CU group, p-tau231 adjusted for demographics showed the strongest association with both Aβ PET (R-squared = 35.73% and AUC = 0.877) and tau PET (R-squared = 35.73% and AUC = 0.877) (Figure 1). In the CI group, GFAP adjusted for demographics showed the strongest association with both Aβ PET (R-squared = 29.04% and AUC = 0.935) and Tau PET (R-squared = 43.94% and AUC = 0.906) (Figure 1).
Conclusions
We showed that plasma p-Tau231, a novel biomarker of early AD, best depicts AD pathophysiology in CU. Interestingly, GFAP, an astrocyte reactivity marker, is better associated with Aβ and Tau PET than plasma p-tau and Aβ markers in CI individuals. Our results highlight - for the first time - that the performance of the novel plasma biomarkers of amyloid, tau, and inflammation to detect brain AD pathophysiology is driven by disease stages.