Multimodal investigation of Tau accumulation and functional connectivity in Alzheimer’s disease

Details

Supervisors

Macq, Benoît ; Dricot, Laurence

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical, à finalité spécialisée

Abstract

enAlzheimer's disease is associated with a progressive accumulation of tau protein and global alterations in large-scale functional brain networks. In recent years, there has been growing interest in how these processes relate to each other, especially in the early stages of the disease. Even though numerous studies have examined tau protein accumulation and functional connectivity, the relationship is still not fully understood. The aim of this research is to establish the association between regional tau aggregation and functional brain connectivity using a multimodal approach, involving the application of both positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI). To assess functional connectivity, lagged cross-correlation analysis was applied to examine the temporal association between regional Blood Oxygen Level Dependent (BOLD) signals, and graph theoretical measures were further used to characterise the functional connectivity. These results suggest an increasing tau deposition across clinical stages, with a clear involvement of areas commonly involved in the early phase of Alzheimer's disease. Functional connectivity showed non-linear trends among clinical stages with initial increases in connectivity within intermediate stages followed by decreases in later stages. Importantly, a significant spatial association was found between functional connectivity and inter-regional tau similarity patterns, suggesting that tau pathology progression might follow functional brain networks. These results are consistent with the network-based transmission theory of tau pathology, emphasising the importance of taking into account the large-scale structure of the brain in Alzheimer's disease. This research enhances our knowledge regarding the underlying disease mechanisms and supports the creation of early biomarkers by combining multiple imaging modalities.