Contribution of mixed pathology to medial temporal lobe atrophy in Alzheimer's disease

Introduction: It is unclear how different proteinopathies (tau, transactive response DNA-binding protein 43 [TDP-43], amyloid beta [A beta] and alpha-synuclein) contribute to atrophy within medial temporal lobe (MTL) subregions in Alzheimer's disease (AD). Methods: We utilized antemortem structural magnetic resonance imaging (MRI) data to measure MTL substructures and examined the relative contribution of tau, TDP-43, A beta, and alpha-synuclein measured in post-mortem tissue from 92 individuals with intermediate to high AD neuropathology. Receiver-operating characteristic (ROC) curves were analyzed for each subregion in order to discriminate TDP-43-negative and TDP-43-positive patients. Results: TDP-43 was strongly associated with anterior MTL regions, whereas tau was relatively more associated with the posterior hippocampus. Among the MTL regions, the anterior hippocampus showed the highest area under the ROC curve (AUC). Discussion: We found specific contributions of different pathologies on MTL substructure in this population with AD neuropathology. The anterior hippocampus may be a relevant region to detect concomitant TDP-43 pathology in the MTL of patients with AD.