HAI Book 2025 - Flipbook - Page 448
Vrillon, Agathe
Association of [18F]Flortaucipir-PET and plasma p-tau217 with tau
neuropathology in AD and other neurodegenerative disorders
Agathe Vrillon1,3, Salvatore Spina1,3, Jhony Mejia-Perez1, Tia Lamore1, Daniel Schonhaut1,
Claire Yballa1, David Soleimani-Meigooni1, Adam Boxer1, Julio Rojas1, Argentina Lario Lago1,
William Jagust1, Bruce Miller1,3, Howard Rosen1,3, William Seeley1,3, Lea Grinberg1,3, Gil
Rabinovici1, Lawren VandeVrede1, Renaud La Joie1,3
1
University of California San Francisco, San Francisco, CA, US
University of California Berkley, Berkley, CA, US
3
Global Brain Health Institute, San Francisco, CA, US
2
Background: Evaluating the relationships between tau imaging and fluid biomarkers with autopsy data is critical
for validating their sensitivity and specificity for Alzheimer9s disease neuropathologic change (ADNC). We aimed
to examine the association between Flortaucipir-PET and AD neuropathology and to characterize the association
between Flortaucipir-PET and plasma ptau-217 levels in autopsy cases.
Method: We analyzed Flortaucipir-PET (acquisition 80-100 minutes post-injection) from 66 patients with a clinical
diagnosis of various neurodegenerative diseases who underwent autopsy at the UCSF Alzheimer9s Disease
Research Center (median age 66 years [range 34-96], 39% female, median PET-to-autopsy delay 3.8 years [range
0.3-8.2]). SUVRs were calculated (reference: inferior cerebellar cortex) in the entorhinal cortex (early tau region)
and the temporal meta-ROI (AD signature region). Semi-quantitative rating of tau neuropathology in six brain
regions was available for n=38 participants. Plasma p-tau217 was measured using Simoa (Janssen®) in n=54
participants (median PET-to-plasma delay 1.4 months [range 0-7]).
Results: Our cohort included 35 patients with autopsy-confirmed AD, 25 with non-AD tauopathies, and 6 with nontau neurodegenerative diseases. Flortaucipir-SUVRs were elevated in patients with a primary neuropathological
diagnosis of AD compared with non-AD patients (Fig.1A). Consistently elevated PET signal was detected in both
the entorhinal cortex and temporal meta-ROI of patients with neurofibrillary tangle (NFT) Braak stage VI (Fig.1B)
and high ADNC levels (Fig.1C). Semi-quantitative levels of NFTs and AD tau gray matter threads were correlated
with local Flortaucipir-SUVRs across cortical regions (Fig.2). Plasma p-tau217 levels were increased in patients
with advanced AD neuropathology (Fig.3A). P-tau217 levels were strongly correlated with Flortaucipir-SUVRs
across ROIs (rg0.75), fully driven by Braak V-VI cases (Fig.3B). Flortaucipir-SUVRs and plasma p-tau217 levels
discriminated AD from non-AD neuropathological diagnosis with similarly high performance (AUC=0.95-0.99
Fig.3C).
Conclusion: Flortaucipir-PET and plasma p-tau217 both displayed strong specificity to advanced AD tau
neuropathology but lacked sensitivity to early AD tau stages.
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