# Down syndrome, early cataracts, eye diseases, and beta-amyloid conformers

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $196,979

## Abstract

PROJECT SUMMARY/ABSTRACT
Down syndrome (DS) is the most common chromosomal disorder with an occurrence of 1 in 700 births. It is, by
far, the leading known cause of intellectual disability. The longevity of DS people has thankfully increased and
several health issues have subsequently emerged, sharing commonality with Alzheimer’s disease (AD). DS is
caused by an additional chromosome to the normal 21st pair (Trisomy 21). Chromosome 21 encodes several
genes contributing to AD; most notably amyloid precursor protein (APP), which is cleaved to form different forms
of beta-amyloid (A). Accumulation of A plaques in the AD brain is one its defining pathologies and A is also
present in the eyes of people with DS. Multiple ocular anomalies, including cataracts, occur at a much higher
frequency starting at younger ages for people with DS. These eye disorders are associated with A, which can
cause oxidative stress and degeneration in the lens epithelial layer.
To carefully understand the contribution and role of A in the eye, we propose to adapt a powerful technology
platform for the discovery of a large panel of nanobodies (Nbs) that can be used as conformer-specific probes
to investigate the histological distribution of A in the eye (retina and lens tissue). These Nbs would allow us to
identify overlooked and potentially rare A oligomeric conformers, which could be important to differentiate
deposits found in DS eyes, perhaps yielding some important insights for AD. Further, some of our Nbs may
sequester and dissolve certain oligomers and aggregates of A, enabling the potential development of novel
therapeutics delivered into the eyes of those with DS and AD. Our specific aims are: (1) discover, produce, and
validate Nbs against different conformations of A protein conformer species and (2) test and validate this panel
of Nbs using eye tissue and lens from AD mouse models recapitulating DS. These Nbs will be valuable reagents
for those studying DS and AD.

## Key facts

- **NIH application ID:** 10018872
- **Project number:** 5R21EY031277-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** GEOFFREY A CHANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,979
- **Award type:** 5
- **Project period:** 2019-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018872

## Citation

> US National Institutes of Health, RePORTER application 10018872, Down syndrome, early cataracts, eye diseases, and beta-amyloid conformers (5R21EY031277-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018872. Licensed CC0.

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