Abstract Details

Title Graphical Model Analysis of Global Amyloid's Impact on Regional Tau Dynamics

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S15 - Innovations in Alzheimer's Diagnostics (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

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.

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.

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.

Authors/Disclosures
Krish B. Kapadia, BS PRESENTER	Mr. Kapadia has nothing to disclose.
Meagan Lauber	Ms. Lauber has nothing to disclose.
Matteo Bellitti, PhD	The institution of Dr. Bellitti has received research support from Framingham Heart Study Brain Aging Program. The institution of Dr. Bellitti has received research support from National Institutes of Health. The institution of Dr. Bellitti has received research support from American Heart Association.
Varuna Jasodanand	Miss Jasodanand has nothing to disclose.
Vijaya B. Kolachalama, PhD, FAHA (Boston University)	Vijaya B. Kolachalama, PhD, FAHA has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AstraZeneca. Vijaya B. Kolachalama, PhD, FAHA has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Altoida. Vijaya B. Kolachalama, PhD, FAHA has stock in CogniScreen Inc.. Vijaya B. Kolachalama, PhD, FAHA has stock in deepPath Inc..

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