The MRI signature of limbic predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) has not been fully determined. In this work, we investigated the association of diffusion anisotropy with LATE-NC in autopsied brains of community-based older adults (N=148). Voxel-wise analysis revealed an independent association of lower fractional anisotropy (FA) with greater LATE-NC burden in medial temporal lobe white matter, controlling for other neuropathologies. The white matter connections implicated include fibers connecting cortical and subcortical regions where LATE-NC is typically found. Comparison of FA values across LATE-NC stages revealed that FA may allow detection of LATE-NC in later stages of the disease.