Graphical Model Analysis of Global Amyloid's Impact on Regional Tau Dynamics
Meagan Lauber1, Matteo Belliti2, Krish Kapadia3, Varuna Jasodonand2, Vijaya Kolachalama4
1Department of Medicine, Boston University School of Medicine; Graduate Program for Neuroscience, Boston University School of Medicine, 2Department of Medicine, Boston University School of Medicine, 3Chobanian and Avedisian Boston University School of Medicine, 4Department of Medicine, Boston University School of Medicine; Faculty of Computing and Data Science, Boston University
Objective:
To analyze the complex interactions between Amyloid-beta (Aβ) and tau in Alzheimer’s disease (AD) using probabilistic graphical models, assessing how regional tau accumulation is influenced by Aβ burden.
Background:
Aβ and hyperphosphorylated tau are crucial biomarkers in AD pathogenesis, interacting synergistically to accelerate disease progression. While Aβ initiates cascades leading to tau hyperphosphorylation and neurofibrillary tangles, PET imaging studies suggest a sequential progression from amyloidosis to tauopathy, closely linked with neurocognitive symptoms.
Design/Methods:
Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Anti-Aβ Treatment in Asymptomatic Alzheimer’s (A4) study were utilized, involving participant across various cognitive stages and employing both Florbetapir and Flortaucipir as tracers. Tau SUVr values were harmonized across studies, and participants were stratified into quantile groups based on Aβ levels. A LASSO regularized Gaussian graphical model (GGM) analyzed partial correlations among brain regions to discern patterns of tau accumulation across different Aβ levels.
Results:
Statistical analyses revealed significant differences in tau structure among low, medium, and high Aβ groups in both ADNI and A4 cohorts, with graph metrics, such as small-world coefficient, indicating increased tau efficiency as Aβ burden increased.
Conclusions:
Our findings indicate that tau accumulates more efficiently with increasing Aβ burden, highlighting an interplay that could inform development of dual-targeting therapies in AD. This study underscores the importance of Aβ and tau interactions in AD progression and supports the hypothesis that targeting both pathologies could be crucial for therapeutic interventions.
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