HAI Book 2025 - Flipbook - Page 309
Lussier, Firoza
62
Longitudinal multicenter head-to-head harmonization of tau PET
tracers: an overview of the HEAD study cohort
Firoza Lussier1, Guilherme Povala1, Guilherme Bauer-Negrini1, Livia Silva do Amaral1, Pamela
Lukasewicz Ferreira1, Bruna Bellaver1, Joseph Masdeu2, Dana L. Tudorascu1, David SoleimaniMeigooni3, Juan Fortea4, Val Lowe5, Hwamee Oh6, Belen Pascual2, Brian A. Gordon7, Pedro
Rosa-Neto8, Suzanne Baker9, Tharick A. Pascoal1
1
University of Pittsburgh, Pittsburgh, PA, US
Houston Methodist Research Institut, Houston, TX, US
3
University of California San Francisco, San Francisco, CA, US
4
Hospital de la Santa Creu i Sant Pau, Barcelona, ES
5
Mayo Clinic, Rochester, MN, US
6
Brown University, Providence, RI, US
7
Washington University in St. Louis, St. Louis, MO, US
8
McGill University, Montreal, QC, CA
9
Lawrence Berkeley National Laboratory, Berkeley, CA, US
2
Background: Standardizing tau pathology quantification in vivo is challenged by differences in binding
characteristics between tau-PET tracers. The HEAD study aims to generate a leading, longitudinal head-to-head
dataset of MK-6240, Flortaucipir, RO948, and PI-2620 tau-PET to harmonize tracers' outcomes and develop tools
for the generalization of findings across studies and trials.
Methods: The HEAD study comprises nine sites across the US, Canada, and Europe, at which study participants
(young/CU/MCI/dementia) undergo tau-PET with at least two tracers, amyloid-PET, MRI, blood collection, and
standardized neuropsychological testing, at baseline and 18-month follow-up. PET and MRI acquisition are based
on ADNI4 protocols and neuropsychological testing employs the NACC Uniform Data Set. The National Centralized
Repository for AD serves as the blood sample biorepository and the Laboratory of Neuroimaging provides a
centralized database for imaging/clinical data archiving.
Results: In 24 months (November 2022-October 2024), 594 active study participants were enrolled in HEAD, with
444 (75%) having completed baseline data collection. Mean age of older adults is 71.6 years, and 23% of individuals
come from underrepresented groups (race/ethnicity/rurality). Thus far, 1,210 head-to-head tau-PET have been
acquired in the HEAD study, using MK-6240, Flortaucipir, PI-2620, and RO948 (mean acquisition window=30.3
days). Over 500 data points of amyloid-PET, MRI, blood, and clinical assessment have additionally been collected
(Fig.1). Representative cases of head-to-head tau-PET with 4 tracers are shown in Fig.2. APOEε4 carriership,
plasma biomarkers (A´42/40 ratio/NfL/GFAP/PTau217), visual rating of amyloid-PET, and Braak stage
classification have been derived from the HEAD cohort, summarized in Fig.3.
Conclusions: The HEAD study cohort represents the largest head-to-head tau-PET dataset to date and
represents a continued effort in the optimization of AD imaging biomarkers. Results being generated from HEAD
study cohort data will provide novel and crucial guidance on the use of tau-PET tracers in research, clinical trials,
and prospectively in clinical practice.
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