# A platform for cell type-level transcriptomic, epigenomic and spatial interrogation of Alzheimer's disease

> **NIH NIH U19** · ALLEN INSTITUTE · 2022 · $250,000

## Abstract

Project Summary Abstract
The spatial and molecular details of cell type vulnerability during Alzheimer’s disease (AD) progression remain
unclear. The objective of this project is to apply spatial profiling methods to brain tissue from donors at multiple
stages of Alzheimer’s disease to describe changes in cell type composition, location, and gene expression as
pathology advances across brain regions. The field of spatial transcriptomics is highly dynamic and rapidly
evolving, with rapid progress and now commercialization that offers the potential to better achieve the original
aims of the project. Multiplexed Error Robust In Situ Hybridization (MERFISH) is a technique capable of
profiling hundreds or thousands of genes in tissue sections, which enables identification of transcriptomically-
defined cell types and provides a quantitative assessment of gene expression without disrupting tissue
structure. Recently a commercially developed version of MERFISH has become available in the form of
MERSCOPE by Vizgen, which provides the benefits of an all-in-one system capable of reliable high throughput
spatial profiling of large tissue sections. The MERSCOPE system represents a significant advance in
technology that was not available at the time of the grant’s funding and can dramatically accelerate the
achievement of our aims to profile changes in tissue microarchitecture associated with AD. Pilot data from this
platform derived from both neurotypical and AD-affected donor brain tissue has shown that this approach is an
effective and comprehensive method for profiling cell type composition and gene expression. Importantly, the
Vizgen MERSCOPE platform is compatible with imaging both gene and protein expression. By combining
immunohistochemistry (IHC) and MERFISH with this system, we will be able to correlate sites of pathological
protein aggregation with proximity to specific cell types at distinct stages of disease. We have developed IHC
chemistry compatible with MERFISH profiling and can combine these methods for use on the MERSCOPE.
The MERSCOPE platform will allow the project to deliver greater scientific impact by significantly accelerating
the original Project 3 grant aims. It will enable us to profile tissue from multiple disease stages rapidly, while
placing cell type and gene expression in the context of disease progression and pathological degeneration of
tissue.

## Key facts

- **NIH application ID:** 10600340
- **Project number:** 3U19AG060909-03S1
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Jennie Leigh Close
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600340

## Citation

> US National Institutes of Health, RePORTER application 10600340, A platform for cell type-level transcriptomic, epigenomic and spatial interrogation of Alzheimer's disease (3U19AG060909-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10600340. Licensed CC0.

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