Hippocampal subfield thickness and shape analysis in examining the impact of TDP-43 in primary age-related tauopathy

INTRODUCTION: Hippocampal subfields are vulnerable to the transactive response DNA-binding protein of 43 kDa (TDP-43) and tau in primary age-related tauopathy (PART). Geometry-based morphometric analysis can improve the detection of structural changes in the hippocampus. METHODS: Forty-seven cases of autopsy-confirmed PART without TDP-43 and 19 cases of PART with TDP-43 underwent antemortem magnetic resonance imaging (MRI) hippocampal segmentation and shape analysis. A separate cohort of 16 younger healthy individuals (YHIs) was included as a reference group. Hippocampal shape was analyzed in Python with non-parametric cluster permutation testing. RESULTS: PART(TDP+) group exhibited thinner left subiculum and CA1, with curvature deformations in left CA1 and CA2/3, relative to PART(TDP-). Both PART groups showed right-sided predominance of thinning in presubiculum and subiculum, as well as curvature deformations in right presubiculum, subiculum, and CA1 when compared to YHIs. DISCUSSION: Geometry-based analysis showed different patterns of hippocampal thinning and curvature associated with PART(TDP+) compared to PART(TDP-).