HAI Book 2025 - Flipbook - Page 134
Cassa Macedo, Arthur
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The spatial spread of tauopathy precedes the increase in tau-PET load
in Alzheimer9s disease
Arthur Cassa Macedo1, Joseph Therriault1, Nesrine Rahmouni1, Cecile Tissot3, Etienne
Aumont1, Yi-Ting Wang1, Stijn Servaes1, Lydia Trudel1, Brandon Hall1, Seyyed Ali Hosseini1,
Jaime Fernandez-Arias1, Gleb Bezgin1, Tevy Chan1, Yansheng Zheng1, João Pedro FerrariSouza2, Pamela CL Ferreira2, Bruna Bellaver2, Firoza Z Lussier2, Tharick A Pascoal2, Pedro
Rosa-Neto1
1
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, CA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, US
3
Lawrence Berkeley National Laboratory, Berkeley, CA, US
2
Background: Spatial extent of tauopathy (SEOT) is a promising outcome measure for trials as it correlates better
with cognition in Alzheimer9s disease (AD) than SUVR. We aimed to track SEOT and SUVR changes in AD-related
areas to understand their temporal relationship.
Methods: We studied 606 cognitively unimpaired and 569 cognitively impaired individuals from two cohorts
(TRIAD and ADNI) using [18F]MK6240 or [18F]AV1451 tau-PET. We derived SUVR as a proxy of tau load, while SEOT
(i.e. proportion of abnormal voxels relative to a reference group) measured spatial spread of tauopathy. 277
participants returned for 2-year follow-up visits. At baseline, we calculated Spearman9s correlations between
SUVR and SEOT in Braak regions. Moreover, amyloid-positive participants were grouped by SEOT range (0-25%,
25-50%, 50-75%, 75-100%) to compare their SEOT and SUVR in the subsequent Braak region. Longitudinally, we
tracked changes in SEOT and SUVR by grouping participants based on their baseline SEOT level (SEOT-HIGH
[g75%] versus SEOT-LOW [
