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

> **NIH NIH U19** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $739,002

## Abstract

Abstract
People with Down syndrome (DS) develop Alzheimer disease (AD) neuropathology, including Aβ plaques and
tau neurofibrillary tangles by the age of 40 years. However, the age of onset of cognitive decline, mild
cognitive impairment (MCI) and dementia can occur over 10 years later, with individual variability in the age of
onset. The overarching goal of ABC-DS is to understand biomarkers that predict conversion from cognitively
stable to MCI or dementia and potentially the age of onset. Biomarkers in ABC-DS includes neuroimaging (MRI
and PET), proteomics, metabolomics and genomics (blood/cerebrospinal fluid/DNA).
In this supplement to ABC-DS, we propose to leverage the neuropathology core's collection of tissue from
brain donations prospectively as well as the legacy autopsy cohort (U01AG051412, R01HD064993) to
accomplish 2 aims: (1) to create an amyloid/tau/neurodegeneration framework (AT(N)) for neuropathology in
clinically characterized cases with age as the dependent variable and (2) to define DS-specific gene
expression changes in a spatially resolved manner. Thus, we are requesting funds to allow us to examine the
brains from 30 people with DS and make comparisons to 20 age matched neuropathology-free controls (from
the NIH Neurobiobank) with tissue being at UCI. Studies for Aim 1 includes a series of immunohistochemical
identification of proteins of interest involving Aβ, tau, neuroinflammation, cerebrovascular pathology as well as
non-AD associated pathologies (e.g. Lewy bodies, TDP-43), in brain regions involved in AD pathogenesis, with
digital pathology and quantification approaches. In parallel using frozen tissue from the same cases, we will
use spatial transcriptomics and the 10X genomics Visium platform to conduct single nucleus RNA sequencing.
The successful completion of these studies will provide a rich dataset that can be shared and made available
to other researchers, permit the testing of hypotheses related to the Projects in U19AG068054, and set the
stage for neuropathology data acquisition in prospective ABC-DS brain donations.

## Key facts

- **NIH application ID:** 10530789
- **Project number:** 3U19AG068054-02S2
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** BENJAMIN L HANDEN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $739,002
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10530789

## Citation

> US National Institutes of Health, RePORTER application 10530789, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) (3U19AG068054-02S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10530789. Licensed CC0.

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