# Modeling Basal Forebrain Cholinergic Neurons in Down syndrome

> **NIH NIH R36** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $72,325

## Abstract

ABSTRACT
Down syndrome (DS), or trisomy 21, is both a complex neurodevelopmental and neurodegenerative
disorder. DS is characterized by altered cortical development resulting in intellectual impairment at birth
and Alzheimer’s disease (AD) pathology in middle age. It is estimated that there are more than 400,000
people living with DS in the U.S. Affecting one in every 700 live births, DS the most common genetic
form of intellectual disability, which ranges from mild to moderate with deficits in domains including
attention and memory. As individuals with DS age, these cognitive functions decline as they develop
AD pathology. A critical feature that links cognitive impairment and neurodegeneration in trisomy 21 is
the population of neurons that are susceptible in both processes: basal forebrain cholinergic neurons
(BFCN). BFCNs play key roles in regulating attention, memory, and learning. Degeneration or
impairment of BFCNs lead to memory loss, decreased spatial recognition, and disturbance in language.
Degeneration of this population has also been well documented in a diverse range of human
neurocognitive disorders, including DS and AD. However, key molecular pathways involved in BFCN
degeneration leading to cognitive, memory and learning deficits aren’t well understood. This project will
explore the unique differences of BFCNs derived from both isogenic control and DS human derived
induced pluripotent stem cells (iPSCs) to better understand the molecular mechanisms that underlie
the susceptibility of this subset of neurons and fill a significant gap in the basic understanding of BFCNs.
Results will provide foundational data for identifying therapeutic targets for DS, as well as have an
impact on our overall understanding of other neurodegenerative diseases such as AD.

## Key facts

- **NIH application ID:** 10428549
- **Project number:** 5R36AG072108-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jose Luis Martinez
- **Activity code:** R36 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,325
- **Award type:** 5
- **Project period:** 2021-06-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428549

## Citation

> US National Institutes of Health, RePORTER application 10428549, Modeling Basal Forebrain Cholinergic Neurons in Down syndrome (5R36AG072108-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10428549. Licensed CC0.

---

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