Association of [ 18 F]Flortaucipir–PET and Plasma p-Tau217 With Tau Neuropathology in Alzheimer Disease and Other Neurodegenerative Disorders

BACKGROUND AND OBJECTIVES: F]flortaucipir tau PET, plasma phosphorylated-tau 217 (p-tau217), and AD neuropathology in a cohort of clinically impaired participants from a tertiary dementia center. METHODS: This was a retrospective study conducted at the University of California San Francisco Neurodegenerative Disease Brain Bank that included all participants with a clinical diagnosis of neurodegenerative disease who underwent antemortem flortaucipir-PET and autopsy from 2013 to 2024. Flortaucipir-PET was acquired 80-100 minutes after injection and normalized to the inferior cerebellar cortex; standardized uptake value ratios (SUVRs) were extracted from the entorhinal cortex (early tau region) and the temporal meta-regions of interest (ROIs) (AD-signature region). Plasma p-tau217 was quantified using Simoa (Janssen) in 56 participants (median [interquartile range, IQR] PET-to-plasma duration: 1.6 months [0.24-3.7]). Semiquantitative rating of AD neurofibrillary tangle (NFT) burden in cortical areas was available for 56 participants. The diagnostic performance of tau PET and plasma p-tau217 was assessed using receiver operating characteristic analysis with cross-validation. RESULTS: 's ≥ 0.75). Both markers identified Braak stage V-VI levels with similarly high performance (entorhinal SUVR, area under the curve [AUC] = 0.92 [95% CI 0.91-0.93]; temporal meta-ROI SUVR, AUC = 0.91 [95% CI 0.90-0.92]; plasma p-tau217, AUC = 0.90 [95% CI 0.89-0.91]), but PET outperformed plasma p-tau217 in identifying high/intermediate ADNCs (entorhinal ROI, AUC = 0.94 [95% CI 0.94-0.95]; temporal meta-ROI AUC = 0.94 [95% CI 0.94-0.95]; plasma p-tau217, AUC = 0.89 [95% CI 0.88-0.90]). DISCUSSION: Flortaucipir-PET and plasma p-tau217 both displayed strong specificity for primary AD neuropathologic diagnosis but limited sensitivity for early tau co-pathology in non-AD diagnoses.