Influence of TDP-43 on temporal lobe diffusion metrics using DTI and NODDI in Alzheimer-related TDP-43 proteinopathy

Motivation: TDP-43 deposition in Alzheimer's disease (AD) is associated with atrophy of the temporal lobe, yet diffusion changes in AD-related TDP-43 proteinopathy are understudied. Goal(s): Evaluate the utility of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) as in-vivo markers for detecting AD-related TDP-43 proteinopathy. Approach: A cross-sectional analysis of temporal lobe DTI and NODDI metrics was conducted in 49 autopsy-confirmed AD cases, comparing TDP-43-positive cases to negative cases. Results: TDP-43-positive cases showed greater diffusion abnormalities in the left hippocampus, amygdala, and uncinate fasciculus, suggesting these metrics can aid in detecting AD-related TDP-43 pathology. Impact: The study demonstrates that TDP-43 significantly affects brain microstructure in AD, particularly in the left temporal lobe, with diffusion changes from DTI and NODDI potentially serving as biomarkers for early detection and diagnosis of TDP-43 in AD.