HAI Book 2025 - Flipbook - Page 305
Hosseini, Seyyed Ali
61
Longitudinal and cross-sectional interplay between astrocyte
activation and ventricular changes promoting Alzheimer9s disease
pathology
Seyyed Ali Hosseini1,2, Stijn Servaes1,2, Nesrine Rahmouni1,2, Etienne Aumont1,2, Joseph
Therriault1,2, Brandon Hall1,2, Yi‐Ting Wang1,2, Arthur C Macedo1,2, Jaime Fernandez Arias1,2,
Gleb Bezgin1,2, Kely Quispialaya Socualaya1,2, Tevy Chan1,2, Lydia Trudel1,2, Yansheng Zheng1,2,
Serge Gauthier1,2, Tharick Ali Pascoal3, Pedro Rosa‐Neto1,2
1
Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, McGill University, Montreal, QC,
Canada, Montréal, QC, CA
2
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, H3A 1A1, Canada, Montréal, QC, CA
3
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA, Pittsburgh, PA,
US
Objectives: Pro-inflammatory astrocyte activation alongside with choroid plexus changes and ventricular
enlargement may alter cerebrospinal fluid (CSF) clearance. Altered clearance could lead to Alzheimer9s disease
through amyloid-´ and tau accumulation. We aimed to verify whether ventricular remodeling and astrocyte
activation drive AD-associated protein aggregation.
Methods: We analyzed data from 500 participants enrolled in the Translational Biomarkers in Aging and Dementia
(TRIAD) cohort at McGill University, totaling 883 imaging sessions. Magnetic Resonance Imaging (MRI) and Positron
Emission Tomography (PET) with [18F]AZD4694 (amyloid-´), [18F]MK6240 (tau), and [11C]PBR28
(Neuroinflammation) tracers were utilized. Choroid plexus and ventricular volumes were segmented using
Freesurfer and adjusted for intracranial volume. Ventricular radioactivity assessed choroid plexus function.
Plasma glial fibrillary acidic protein (GFAP) levels were used to measure astrocyte activation. Associations
between ventricular remodeling, GFAP levels, and amyloid-´ and tau loads were analyzed using region-of-interest
and voxel-wise methods.
Results: We observed significant reductions in ventricular radioactivity, alongside increased choroid plexus and
ventricular volumes with amyloid-´ and tau pathology (Fig. 1). The [18F]MK6240 time activity curves in the lateral
ventricles shows choroid plexus function with the initial peak. Marked initial uptake differences were found
among the CN (Y), A-T-, A-T+, and A+T+ groups (fig1a). Voxel-wise analyses revealed that amyloid-´ and tau
accumulation were significantly associated with ventricular volume and GFAP levels (Figs. 233). Kaplan-Meier
survival analysis further demonstrated that third tertiles of GFAP, ventricular volume, and choroid plexus volume
underwent faster cognitive decline, with significant differences between tertiles (Fig. 4). These effects persisted
after adjusting for amyloid and tau loads, without evidence of interaction or mediation (Fig. 3).
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