HAI Book 2025 - Flipbook - Page 401
Moret, Sophia
98
Hemispheric lateralization of tau-related network dysfunction and its
association with neuropsychiatric symptoms in preclinical Alzheimer9s
disease
Sophia Moret1, Raina Vin1, Carolyn Fredericks1
1
Yale University, New Haven, CT, US
Background: Neurofibrillary tau tangles are one of the hallmark biomarkers of Alzheimer9s Disease (AD). In
symptomatic AD, tau pathology shows temporal lobe asymmetry, with greater right-hemisphere tau linked to
more severe behavioral symptoms on the Neuropsychiatric Inventory (NPI) (Younes et al., 2024). However, the
effects of tau on hemispheric connectivity and its direct relationship with neuropsychiatric symptoms in the
preclinical stages remain unclear.
Methods: We used a preclinical dataset (n=260 amyloid-positive participants in the Anti-Amyloid Treatment in
Asymptomatic Alzheimer9s Disease (A4) study) to investigate hemispheric differences in regional tau uptake,
functional connectivity, and their associations with anxiety and depression severity. Structural and functional MRI
and tau PET data were parcellated using the Human Brainnetome Atlas. We computed a novel graph-theoretic
metric, tau-weighted node strength (NS), defined as the product of each node9s regional tau uptake and its
functional connectivity with regions in the ipsilateral hemisphere. Spearman correlations were performed
between tau-weighted NS and anxiety and depression scores and were repeated using tau uptake alone. All
correlations were corrected for multiple comparisons using false discovery rate.
Results: Our results show significant correlations between depression scores and tau-weighted NS particularly in
limbic regions, including the caudal temporal thalamus (p=0.003), anterior hippocampus (p=0.006), and
paracentral lobule (p = 0.003). Anxiety scores significantly correlated in limbic and somatosensory regions, such
as the anterior hippocampus (p=0.002), paracentral lobule (p=0.003), and postcentral gyrus (p=0.050). Notably,
there were more significant correlations in the right hemisphere (Figure 1). Regional tau uptake alone did not
exhibit significant correlations with either metric.
Conclusions: These findings suggest that tau-related network disruptions are associated with specific
neuropsychiatric symptoms. Our work reveals an association between hemispheric lateralization of tau pathology
and neuropsychiatric symptoms. Future analyses will explore whether similar tau-driven hemispheric
lateralization connectivity patterns are associated with neuropsychiatric scores in symptomatic AD.
HAI2025 - 401
