# Deciphering HSA21 genes associated with Alzheimers disease in Down Syndrome

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $281,948

## Abstract

Summary
Down syndrome arises from the triplication of a subset of genes on chromosome 21 (HSA21). Individuals with
DS uniformly demonstrate some degree early onset Alzheimers disease. Recent studies have suggested
triplication of genes on HSA21, other than APP, contribute to the disruption of beta amyloid (Abeta) processing
in mice. Whether similar pathological mechanisms are observed in human DS cells, as well as what subset of
HSA21 genes are responsible for this disruption, remain unknown. We have developed a simple but novel
approach using CRISPR gene editing techniques and DS cell culture models which will allow for knockdown of
a single HSA21 copy, while leaving the other two copies intact. With this approach, we can systematically
identify the subset of HSA21 genes most likely to contribute to the altered Abeta processing. Identification of
the subset of HSA21 genes most responsible for AD in DS is not only critical for understanding pathological
mechanisms, but also for devising appropriate therapies for treatment of this disorder.

## Key facts

- **NIH application ID:** 10120793
- **Project number:** 3R21NS115593-02S1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** VOLNEY L SHEEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $281,948
- **Award type:** 3
- **Project period:** 2019-09-15 → 2023-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120793

## Citation

> US National Institutes of Health, RePORTER application 10120793, Deciphering HSA21 genes associated with Alzheimers disease in Down Syndrome (3R21NS115593-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10120793. Licensed CC0.

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