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Three-dimensional histology reveals dissociable human hippocampal long axis gradients of Alzheimer's pathology.


ABSTRACT:

Introduction

Three-dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without an MRI reference. We implemented Path2MR with post-mortem hippocampal sections to explore pathology gradients in Alzheimer's Disease.

Methods

Blockface photographs of brain hemisphere slices are used for 3D reconstruction, from which an MRI-like image is generated using machine learning. Histology sections are aligned to the reconstructed hemisphere and subsequently to an atlas in standard space.

Results

Path2MR successfully registered histological sections to their anatomical position along the hippocampal longitudinal axis. Combined with histopathology quantification, we found an expected peak of tau pathology at the anterior end of the hippocampus, while amyloid-β displayed a quadratic anterior-posterior distribution.

Conclusion

Path2MR, which enables 3D histology using any brain bank dataset, revealed significant differences along the hippocampus between tau and amyloid-β.

SUBMITTER: Ortega-Cruz D 

PROVIDER: S-EPMC10723286 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Three-dimensional histology reveals dissociable human hippocampal long axis gradients of Alzheimer's pathology.

Ortega-Cruz Diana D   Bress Kimberly S KS   Gazula Harshvardhan H   Rabano Alberto A   Iglesias Juan Eugenio JE   Strange Bryan A BA  

bioRxiv : the preprint server for biology 20231207


<h4>Introduction</h4>Three-dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without an MRI reference. We implemented Path2MR with post-mortem hippocampal sections to explore pathology gradients in Alzheimer's Disease.<h4>Methods</h4>Blockface photographs of brain hemisphere slices are used for 3D reconstr  ...[more]

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