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Abstract #4089

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

Anna Lavrova1, Nha Trang Thu Pham 1, Robert Reid1, Bradley Boeve 1, David Knopman 1, Ronald Petersen 1, Aivi Nguyen 1, Ross Reichard 1, Dennis Dickson2, Clifford Jack1, Jennifer Whitwell 1, and Keith Josephs1
1Mayo Clinic, Rochester, MN, United States, 2Mayo Clinic, Jacksonville, FL, United States

Synopsis

Keywords: Dementia, Neurodegeneration, Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, TAR DNA binding protein 43, LATE-NC

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.

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Keywords