# Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)

> **NIH NIH U19** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $250,000

## Abstract

Abstract
Metabolomics is an emerging area of systems biology which aims to comprehensively analyze a wide array of
metabolites in biological samples. The metabolome consists of a vast number of different classes of compounds,
such as amino acids, lipids, organic acids and nucleotides. Elucidation of metabolic alterations using liquid
chromatography (LC) coupled with mass spectrometry (MS) has increased our understanding of early pathway
perturbations associated with neurodegeneration and enabled the development of predictive biomarkers of pre-
clinical dementia. The overarching goal of the parent ABC-DS (Alzheimer’s Biomarkers Consortium - Downs
Syndrome) award is to characterize Alzheimer’s disease (AD) in people with Down syndrome (DS); specifically
projects 2 and 3 aim to translate outcomes to a precision medicine framework and expedite clinical trials via
harmonization of clinical and neuropsychological outcomes with biofluid characterization and genetic measures.
However, identification, verification and validation of blood based biomarkers specific to AD pathology is
constrained by matrix effects and a large linear dynamic range that obscures the ionization and detection of low
abundance compounds that could otherwise be powerful indicators of onset and progression of pre-clinical
dementia in the DS cohort.
We are requesting funds for the purchase of the 7500 QTrap® LC-MS/MS system (7500 QTrap hereafter), a next
generation triple quadrupole mass spectrometer (MS) that is urgently needed for expanding our quantitative MS
capabilities for the ABS-DS consortium projects. Our recent work has shown that metabolites belonging to
energy metabolism and beta-oxidation pathways show significant dysregulation in people with DS and AD. The
requested 7500 QTrap will help to strengthen biomarker discovery, verification and validation workflows for
proposed biomarker studies detailed in Projects 1, 2 and 3 of the ABC-DS program. This equipment supplement
will be used to primarily support our NIA-funded U19 (1U19AG068054-01) project by prioritizing U19 samples
for analysis. When available, it may be used in other program related studies, such as our NIA-funded
(R01AG058644) project. This system combines the requisite attributes of speed, robustness, dynamic range,
and minimization of cross-contamination that is necessary for successful quantitative interrogation of
metabolomic samples using LC-MS.
The 7500 QTrap will be a significant technological advancement for targeted metabolomics workflows due to
dramatic enhancements in sensitivity (102 to 104) and resolution as well as improved analytical pipelines for
downstream data analysis and processing. Taken together, this would augment the detection of small molecules
with improved sensitivity and expand the scope of biofluid biomarker characterization objectives of the parent
award, in compliance with the FDA-MDDT program for developing biomarkers with translational value. This
instrument will be housed at ...

## Key facts

- **NIH application ID:** 10454470
- **Project number:** 3U19AG068054-02S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** BENJAMIN L HANDEN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454470

## Citation

> US National Institutes of Health, RePORTER application 10454470, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) (3U19AG068054-02S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10454470. Licensed CC0.

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