# An Automated platform for 3D reconstruction and profiling of post-mortem Alzheimer's Disease brains

> **NIH NIH R43** · TISSUEVISION, INC. · 2021 · $478,759

## Abstract

PROJECT SUMMARY
AD is a complex, progressive neurodegenerative disease and is the most common cause of
dementia among the elderly. It has a clear spatial and temporal progression; multiple lines of
evidence show that the degeneration patterns seen in AD are not random but show a
characteristic anatomical sequence as the pathology advances over decades. The mechanisms
that cause these spatial patterns are poorly understood and basic questions about the relative
contributions of microscopic molecular mechanisms versus macroscopic anatomical changes in
driving AD progression remain unclear.
Unfortunately, whole brain techniques like MRI lacks the necessary molecular contrast and
resolution to answer these questions. Histology can reveal the microscopic, molecular
signatures, but is constrained to small 2D sections due to technical limitations with large scale
histology, particularly 3D histology. These limitations make it difficult to map AD progression
and limit the usefulness of post-mortem tissue that might reveal crucial clues about AD.
In this proposal we will address this barrier by providing a fee-for-service sectioning, slice
mounting, staining, and imaging platform that will offer non-specialized labs the ability to
obtain high quality 3D serial section reconstructions of post-mortem human brains up to entire
hemispheres. Specimens can be sent to TissueVision where they will be sectioned at thicknesses
ranging from 50 microns to 2 mm, with alternating block face imaging between sections to help
facilitate 3D reconstruction. Each mounted section is available for further staining and
digitization at high resolution with Whole Slide imaging (WSI) and served over the cloud to the
client with optional 3D modeling. The physical sections can be returned to the client or stored
for further follow-up analyses.
This proposal combines expertise in microscopy and 3D histology at TissueVision with world-
class clinical researchers at Indiana University and builds on existing work at TissueVision. The
section capture and slide mounting is based on existing technology contained within our
TissueCyte 1600FC STPT platform for mouse and rat brains. We also build on a strong
collaboration with Jackson Labs and the MODEL-AD center with an existing TissueVision Phase
II NIA SBIR to map AD spatial progression in mouse model brains. We will extend the
collaboration to clinical collaborators at the Model-AD at Indiana University who will be
supplying post-mortem human tissue and providing guidance and feedback on the histological
quality. While our focus is on AD in this project, the proposed technology will have broad impact
across a wide range of disciplines, from cardiac biology, infectious diseases, cancer, and basic
research.

## Key facts

- **NIH application ID:** 10395363
- **Project number:** 1R43AG076342-01
- **Recipient organization:** TISSUEVISION, INC.
- **Principal Investigator:** Timothy M. Ragan
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $478,759
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395363

## Citation

> US National Institutes of Health, RePORTER application 10395363, An Automated platform for 3D reconstruction and profiling of post-mortem Alzheimer's Disease brains (1R43AG076342-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10395363. Licensed CC0.

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