Preclinical research on Alzheimer’s disease

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Table of contents

Introduction
1 Context
1.1 Histology
1.1.1 Principles and evolution
1.1.2 Histology imaging
1.1.3 Histopathological biomarkers quantification
1.2 Alzheimer’s disease
1.2.1 Impact on public health
1.2.2 Pathological hypotheses
1.2.3 Preclinical research on Alzheimer’s disease
1.3 Motivation
2 High-throughput 3D histopathology
2.1 Large-scale tissue section processing
2.2 Whole-slide imaging strategies
2.3 Brain multi-modal 3D reconstruction
2.4 Supervised segmentation of neuropathological markers
3 Brain-wide quantitative analysis of neuropathological markers
3.1 Ontology-based analysis
3.1.1 3D mouse brain atlases
3.1.2 Atlas registration to histopathological data
3.1.3 Mouse brain ontology
3.2 Voxel-wise analysis
3.2.1 Principle and issues for histopathological data analysis
3.2.2 Heat map generation
3.2.3 Cluster detection with simulated data
4 Applications in mouse models of A deposition
4.1 Context of the studies
4.2 Study 1: animal model characterization
4.2.1 Experimental procedures
4.2.2 Ontology-based characterization of A deposition
4.3 Study 2: preclinical immunotherapy evaluation
4.3.1 Experimental procedures
4.3.2 Whole-brain therapeutic intervention evaluation
4.3.3 3D versus 2D histopathology comparison
4.4 Study 3: gene eect evaluation
4.4.1 Experimental procedures
4.4.2 Image processing
4.4.3 ADAM30 eect on A pathology
4.4.4 Discussion
5 Towards multimodal and multiscale analysis
5.1 Matching quantitative 3D histopathology to in vivo MRI
5.2 3D whole-brain histopathology at the cellular-scale
5.2.1 Spatial correlation between cellular markers at the wholebrain level
5.2.2 A hierarchical Gaussian Mixture Model (GMM) approach for touching cells segmentation
Conclusion
A 3D Histopathology Analysis Pipeline (3D-HAPi)
B Experimental procedures summary
C Publications