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

PART with TDP-43 showed thinner left subiculum and CA1 compared to PART without TDP-43.

• 47 cases of autopsy-confirmed PART without TDP-43 and 19 cases of PART with TDP-43 were analyzed.
• Hippocampal subfield segmentation was performed on antemortem MRI scans.
• The thinning differences were lateralized to the left hemisphere.
• Shape analysis was performed in Python with non-parametric cluster permutation testing.

PART with TDP-43 exhibited curvature deformations in left CA1 and CA2/3 relative to PART without TDP-43.

• Curvature deformations were identified using geometry-based morphometric analysis.
• Deformations were observed specifically in left CA1 and CA2/3 subfields.
• Non-parametric cluster permutation testing was used to detect these differences.
• These deformations were distinct from those seen in PART without TDP-43.

Both PART groups showed right-sided predominance of thinning in presubiculum and subiculum compared to younger healthy individuals.

• A separate cohort of 16 younger healthy individuals (YHIs) was included as a reference group.
• Thinning was observed in right presubiculum and subiculum in both PART groups relative to YHIs.
• This right-sided predominance was present regardless of TDP-43 co-pathology status.
• Both PART groups were compared against the YHI reference cohort.

Both PART groups showed curvature deformations in right presubiculum, subiculum, and CA1 when compared to younger healthy individuals.

• Right-sided curvature deformations were identified in presubiculum, subiculum, and CA1.
• These deformations were shared between PART(TDP+) and PART(TDP-) groups relative to YHIs.
• The presence of curvature deformations in both groups suggests a common effect of PART pathology independent of TDP-43.
• Geometry-based shape analysis was used to detect these curvature changes.

Geometry-based analysis revealed different patterns of hippocampal thinning and curvature associated with PART with TDP-43 compared to PART without TDP-43.

• PART(TDP+) showed predominantly left-sided subfield changes while shared changes between PART groups versus YHIs were right-sided.
• The distinct pattern in PART(TDP+) included subiculum, CA1, and CA2/3 subfields on the left.
• This differentiation suggests TDP-43 co-pathology contributes additional and lateralized hippocampal structural changes beyond tau alone.
• Non-parametric cluster permutation testing in Python was the analytical method used to identify these differential patterns.