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

> **NIH NIH U19** · ALLEN INSTITUTE · 2022 · $9,590,782

## Abstract

ABSTRACT (OVERALL)
Our understanding of the neuropathology in Alzheimer’s disease is crude and largely centered on characteristic
deposition of a few pathological proteins. Catalyzed by the BRAIN Initiative, a new generation of molecular tools
to characterize the transcriptome, epigenome and spatial organization of single cells in complex brain tissues is
rapidly revolutionizing our understanding of the diversity of cell types and their selective genetic profiles. These
tools are applicable to postmortem human brain tissues and promise to expand our understanding of the core
cellular and molecular correlates and mechanisms underlying Alzheimer’s disease. The goal of the proposed
Center is to bring together experts in Alzheimer’s disease research and large-scale molecular/anatomical brain
mapping to modernize Alzheimer’s disease tissue banking methods, and to combine traditional and quantitative
neuropathology with emerging single nucleus transcriptomics, single nucleus epigenomics and spatial
transcriptomics technologies. Applied to clinically typical Alzheimer’s cases of varying severity in an iterative and
adaptive design, these techniques are expected to identify increasingly refined molecular pathways associated
with specific neuronal and non-neuronal cell types and yield valuable insights into cell-type selective vulnerability
or resistance to pathology. This increased resolution of AD pathology in terms of cell types and molecular
pathways should provide mechanistic insights and hypotheses on disease initiation and progression, which we
aim to use to catalyze the AD research community through the creation of an open access data resource linked
with other large-scale brain mapping efforts. This Center framework is designed to be extensible to additional
data modalities and technological advances as well as broader cohorts representing Alzheimer’s disease
subtypes and Alzheimer’s disease related disorders in the future.

## Key facts

- **NIH application ID:** 10375357
- **Project number:** 5U19AG060909-03
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Jennie Leigh Close
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $9,590,782
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375357

## Citation

> US National Institutes of Health, RePORTER application 10375357, A platform for cell type-level transcriptomic, epigenomic and spatial interrogation of Alzheimer's disease (5U19AG060909-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375357. Licensed CC0.

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