HAI Book 2025 - Flipbook - Page 257
Fonseca, Corrina
Spatial patterns of voxel-wise tau accumulation across the Alzheimer9s
disease spectrum
Corrina Fonseca1, Renaud La Joie2, Yishu Chao1, Gil Rabinovici2, William Jagust1, Theresa
Harrison1
1
Department of Neuroscience, University of California Berkeley, Berkeley, CA, US
Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience, University of California San
Francisco, San Francisco, CA, US
2
Background: Cross-sectional tau deposition has been described by Braak staging, but how patterns of tau spread
evolve over time and the factors driving longitudinal changes remain unclear. We used whole-brain voxel-wise
analyses to examine longitudinal tau accumulation patterns and their associations with demographics, APOE, and
baseline Alzheimer's disease (AD) pathology across the spectrum from normal aging to clinical AD.
Methods: 1,426 flortaucipir (FTP) scans in 583 participants were included from 4 studies: BACS, ADNI, HABS, and
UCSF (Table 1). Voxel-wise FTP SUVR slope maps were generated to explore whole-brain tau accumulation
patterns within clinical diagnostic groups and associations with age, sex, APOEε4, baseline A´ and tau status, and
baseline global A´ and tau (entorhinal cortex [ERC] and inferior temporal gyrus [ITG]). T-tests and multiple
regression were performed in cognitively normal participants and full sample separately.
Results: Longitudinal voxel-wise tau accumulation patterns resembled Braak staging, progressing from the
medial temporal lobe to temporoparietal and frontal regions in more advanced clinical stages (Figure 1). APOEε4,
A´ positivity, and ERC tau positivity were associated with faster tau accumulation in temporal, parietal, and
frontal regions. Baseline global A´, ERC tau, and ITG tau were key predictors of tau accumulation in progressively
higher neocortical Braak regions (Figure 2). Interactions between A´ and ERC and ITG tau suggested synergistic
effects on tau accumulation in downstream Braak regions across the spectrum. Voxel-wise tau accumulation in
temporoparietal and frontal regions was more strongly linked to lower hippocampal volume and MMSE at the end
of the tau follow-up period compared to baseline measures.
Conclusions: This data-driven, voxel-wise approach to spatially map tau accumulation revealed that the evolution
of the typical pattern of tau deposition is driven by APOE genotype, Ab, and tau in ERC and ITG. These findings
may guide future trials targeting the accumulation tau pathology.
HAI2025 - 257
