# Early cognitive decline in Down syndrome - Supplement

> **NIH NIH R01** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2021 · $268,686

## Abstract

ABSTRACT
Down syndrome (DS) is a caused by an error in cell division resulting in an extra copy of
chromosome 21. The outcome is intellectual disability, physical features, and several medical
vulnerabilities. Further, DS is associated with accelerated aging processes and very high risk for
Alzheimer’s disease (AD). The classic components of AD neuropathology - amyloid plaques and
neurofibrillary tangles (NFTs) – are both affected by overexpressed genes that are on chromosome
21. One of these genes is APP, which produces amyloid beta (Aβ) precursor protein and, can, in
abundance, result in harmful buildup of Aβ deposits (plaques) in the brain. Several other genes that
are on chromosome 21, including DYRK1A, contribute to buildup of Aβ deposits and tau deposits
(NFTs) as well as neuroinflammation and elevated cholesterol - all of which contribute to AD. To date,
it is known that cognitive decline in DS can be detected in adults with DS who are in their 30’s and
40’s, and some declining functions are predictive of later AD diagnosis. We argue that some declines
may be detectable at an earlier age, especially because AD neuropathology begins well before age
20 years in those with DS. Thus, in our parent R01 study, Early Cognitive Decline in Down Syndrome
(R01HD098179), we examine decline over three years in cognitive, language, and behavioral
functions in adolescents and young adults, age 15-25 years. If decline can be detected at this young
age, it may be possible to develop preventive therapeutics that can potentially improve quality of life
and slow the progression of early aging and AD in individuals with DS. The broad, long-term goal of
the present supplement project is to add blood collection and banking to the parent study.
Blood-based biomarkers that are associated with AD may help distinguish between early declines
that are symptoms of accelerated healthy aging and early declines that are symptoms of pre-clinical
AD. Aim 1 of the 1-year supplement project is to collect and bank blood samples from participants
with Down syndrome at Time 1 of the parent study. All participants with DS who are enrolled in the
parent study (N = 60) will be invited for blood draw at Time 1 of the parent study. Blood will be banked
at University of California Davis. Aim 2 is to quantify biomarkers from the blood samples and create a
dataset of biomarker indices. The biomarkers of interest include amyloid beta, tau, and DYRK1A
protein; as well as Neurofilament Light, inflammatory markers, cholesterol/lipid levels, thyroid levels,
and APOE polymorphisms. When the parent study has been completed, the biomarker data will be
analyzed along with the behavioral data from the parent study to identify declines that are related to
early progression to AD.

## Key facts

- **NIH application ID:** 10403731
- **Project number:** 3R01HD098179-02S1
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** FRANCES A CONNERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $268,686
- **Award type:** 3
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403731

## Citation

> US National Institutes of Health, RePORTER application 10403731, Early cognitive decline in Down syndrome - Supplement (3R01HD098179-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10403731. Licensed CC0.

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