# Brain Single-nuclei and iPS-derived cells transcriptomic analysis to define the contribution of neuronal and glial pathw

> **NIH NIH R56** · WASHINGTON UNIVERSITY · 2021 · $719,094

## Abstract

Abstract
Alzheimer’s disease (AD) is a complex and heterogenous condition in which multiple molecular pathways are
disrupted in different cell-types and lead to disease. Genetic findings indicate that amyloid-beta protein clearance
and degradation pathways, cholesterol metabolism and the immune system are associated with AD etiology.
However, the specific mechanism, genes and molecular networks have not yet been completely identified.
Single-nuclei transcriptomic (snRNA-seq) data from human brains provides a detailed molecular atlas to study
the pathways dysregulated in AD. We propose to deepen our understanding of the genes, network and
molecular pathways associated with AD by sequencing a high-number of neuronal and glial cells (approximately
3.3 million cells) from human brain carriers of key genetic mutations and high risk variants, non-carrier sporadic
AD cases and neuropath-free controls. We will leverage a unique collection of human tissue from the Dominantly
Inherited Alzheimer Network and Knight-ADRC brain banks, and select +220 brains to perform systematic cell-
type specific transcriptomic analyses. This is a unique and innovative study designed to analyze cell-specific
transcriptomic dysregulation in carriers of high effect risk variants (TREM2 and APOE) and fully penetrant
pathogenic mutations in APP/PSEN1/PSEN2 and by comparing them to sporadic AD cases and neuropath-free
controls. This is a powerful approach to address disease heterogeneity, and will provide highly informative
insights into the biology and pathology of neurodegeneration. Replication of these findings will be performed in
snRNA-seq data from induced pluripotent stem cell derived neurons, astrocytes, and microglia-like cells that will
be genome edited to add/remove genetic variants, as well as datasets that are being publicly released. Finally,
we will create a knowledge portal in which all of the processed snRNA-seq data from our study will be harmonized
with that of other research groups to provide a comprehensive molecular atlas that will provide additional insights
into the biology and pathology of AD for the entire research community.

## Key facts

- **NIH application ID:** 10302162
- **Project number:** 1R56AG067764-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Carlos Cruchaga
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $719,094
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302162

## Citation

> US National Institutes of Health, RePORTER application 10302162, Brain Single-nuclei and iPS-derived cells transcriptomic analysis to define the contribution of neuronal and glial pathw (1R56AG067764-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10302162. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*