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

## TL;DR

This study examines how TDP-43 affects hippocampal structure in a brain disease called primary age-related tauopathy, finding distinct patterns of thinning and shape changes.

## Contribution

The study introduces geometry-based morphometric analysis to detect hippocampal subfield changes in primary age-related tauopathy with and without TDP-43.

## Key findings

- PART cases with TDP-43 show thinner left subiculum and CA1 with curvature deformations in left CA1 and CA2/3.
- Both PART groups exhibit right-sided thinning and curvature changes in presubiculum and subiculum compared to younger healthy individuals.

## Abstract

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.

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.

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.

Geometry‐based analysis showed different patterns of hippocampal thinning and curvature associated with PART(TDP+) compared to PART(TDP–).

Geometry‐based unfolding algorithm applied to hippocampal subfield analysis.Primary age‐related tauopathy (PART) cases show reduced thickness in the presubiculum and subiculum.Right hippocampal subfields show stronger thinning and curvature changes.Transactive response DNA‐binding protein positive (TDP+) cases reveal thinning in the left subiculum and CA1 versus TDP−.Curvature deformations in CA1 and CA2/3 with TDP of 43 kDa (TDP‐43) presence.

Geometry‐based unfolding algorithm applied to hippocampal subfield analysis.

Primary age‐related tauopathy (PART) cases show reduced thickness in the presubiculum and subiculum.

Right hippocampal subfields show stronger thinning and curvature changes.

Transactive response DNA‐binding protein positive (TDP+) cases reveal thinning in the left subiculum and CA1 versus TDP−.

Curvature deformations in CA1 and CA2/3 with TDP of 43 kDa (TDP‐43) presence.