HAI Book 2025 - Flipbook - Page 261
Rahmouni, Nesrine
PET astroglia and microglia follow tau propagation patterns in Alzheimer9s
Disease
Nesrine Rahmouni1, Ali Hosseini1, Lydia Trudel1, Etienne Aumont1, Arthur Macedo1, Gleb
Bezgin1, Brandon Hall1, Joseph Therriault1, Yi-Ting Wang1, Jaime Fernandez Arias1, Stijn
Servaes1, Jenna Stevenson1, Ryuichi Harada5, Nobuyuki Okamura5, Andrea Lessa Benedet3,
Eduardo R. Zimmer4, Tharick Pascoal2, Pedro Rosa-Neto1
1
McGill University, Montreal, QC, CA
University of Pittsburgh, Pittsburgh, PE, US
3
University of Gothenburg, Gothenburg, SE
4
Universidade Federal do Rio Grande do Sul, Porto Alegre, BR
5
Tohoku Medical and Pharmaceutical University, Sendai, JP
2
Background: Glial responses affect Alzheimer9s disease (AD) pathophysiology. However, prior studies of in-vivo
typically provide partial appraisals of tau distribution focusing either on microglia or astrocytes. Here, we
investigated the associations between astroglia and microglia with amyloid and tau, across the AD spectrum
using PET.
Methods: We included 18 individuals from the TRIAD cohort (8 A´ positive). A´ deposition, tau tangles, microglial
activation (TSPO) and astrocyte reactivity (MAO-B) were assessed via [18F]AZD4694-PET, [18F]MK6240-PET,
[11C]PBR28- PET and [18F]SMBT-1-PET respectively. Voxel-based regression models evaluated the association of
[18F]SMBT-1-PET in the precuneus with amyloid-PET, tau-PET and TSPO-PET. We explored the voxelwise
colocalization of microglial activation and astrocytes reactivity9s spatial extent by seeding in Braak I and V. Finally,
we ran network analysis for the 4 tracers using SUVR uptake in (1) Braak regions and (2) amyloid-PET staging
regions.
Results: Tau-PET and [18F]SMBT-1 SUVR in the precuneus were positive associated through the whole cortex,
most strongly in Braak V and VI. Positive associations with TSPO-PET were mainly restricted to the frontal cortex.
No associations with amyloid-PET were significant (Fig.1). Similar spatial extent signatures were found between
MAO-B-PET and TSPO-PET when seeding in Braak I and V (Fig.2A,B), with the highest associations in mid-to-late
Braak regions. Network matrices revealed that the rates of cross-sectional tau propagation correlated
hierarchically with each other according to the Braak stages for microglia- astroglia- and tau-PET and the
elements of each matrix positively correlated with each other (Fig.3A). Microglia and astroglia matrices9 elements
did not correlate with amyloid-PET matrix elements(Fig.3B).
Conclusion: This is the first PET study addressing the associations between amyloid, tau, TSPO and MAO-B in the
same individuals. Our study highlights the colocalization between microglial activation, astrocytes reactivity and
tau accumulation within specific Braak stages.
HAI2025 - 261
