# 3D spatial single-cell multiomics mapping of Alzheimer's disease

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $270,116

## Abstract

Abstract
Tremendous progress has been made in defining Alzheimer’s disease (AD)-associated cell types by single-cell
sequencing approaches, such as scRNA-seq. However, the nucleic-acid–based methods are blind to proteins.
Therefore, AD’s proteome and post-translational modifications (PTMs) remain largely unknown. Another
limitation of single-cell sequencing is that the standard cell isolation techniques damage the fine projections of
brain cells, such as the dendrites of neurons. Missing biomolecules in these brain-cell-specific structures will
seriously mislead our understanding of molecular mechanisms of AD progression. There is an urgent need for
new technologies to fill the technical gaps in the proteomics and multiomics analysis of AD. Here, we bring to
the AD field our NIH Director’s New Investigator Award-winning method, Gel-based Optical-isolation 3D (GO3D)
multiomics. It can precisely dissect tiny projections of brain cells from whole-mount brains for subsequent mass
spectrometry analysis and next-generation sequencing. This method is an ideal approach to achieving my long-
term goal: creating a single-cell-type multiomics map of AD. As the first step, this project focuses on one critical
AD-associated cell type, the astrocyte. We will use GO3D single-cell-type multiomics to identify AD-associated
proteins and PTMs in astrocytes (Aim 1) and establish a multiomics map of AD featuring astrocytes (Aim 2).
5xFAD mouse models at different time points will be used to examine AD in the early, middle, and late stages.
Human prefrontal cortex tissues will be used to validate key discoveries made from mice. Unbiased profiling of
the proteins together with RNAs and chromatin accessibility in astrocytes will provide a list of AD-associated
proteins and PTMs and their regulatory mechanisms, and thus will greatly advance our understanding of the
molecular basis of AD.

## Key facts

- **NIH application ID:** 10939938
- **Project number:** 3DP2GM150017-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Xiaoyu Shi
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $270,116
- **Award type:** 3
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939938

## Citation

> US National Institutes of Health, RePORTER application 10939938, 3D spatial single-cell multiomics mapping of Alzheimer's disease (3DP2GM150017-01S1). Retrieved via AI Analytics 2026-06-05 from https://api.ai-analytics.org/grant/nih/10939938. Licensed CC0.

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