# Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)-04 Supplement 4

> **NIH NIH U19** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $177,627

## Abstract

ABSTRACT
 This is an application for a 1-year administrative supplement to U19 AG068054 “Alzheimer
Biomarker Consortium – Down Syndrome” (ABC-DS, PI: B. Handen, E. Head). This “analysis-only”
proposal will build upon an impressive body of multidisciplinary work that has utilized Positron Emission
Tomography (PET) imaging of individuals with Down Syndrome (DS) to reveal age-related, DS-specific,
and Alzheimer’s disease (AD)-related neuropathophysiological changes in FDG metabolism and
amyloid-beta (Aβ) and tau protein deposition. The emergence and progression of AD in DS has been an
important focus of many of these studies that were performed in large part by members of the ABC-DS
consortium. In this research, we will develop a multivariate multimodal analysis framework that will
better leverage the complexity and richness of multimodal neuroimaging datasets to provide improved
spatiotemporal mapping of Aβ and tau accumulation and enable more sensitive detection of early and
progressive pathophysiological changes in DS, relative to prior assessments. The specific aim is to
perform joint pattern analyses of baseline and longitudinal Aβ and tau PET neuroimaging data acquired
in sibling controls and individuals with DS to identify spatiotemporal patterns of Aβ and tau uptake that
are more sensitive to progressive pathophysiological brain changes, than prior methods. We will apply
multiset canonical correlational analysis (MCCA) and orthogonal signal correction (OSC) to Aβ and tau
data acquired at baseline and 16-month longitudinal follow-up in sibling controls and individuals with DS
(across the continuum of cognitively stable, mild cognitive impairment, and AD continuum). We will
evaluate these patterns with consideration of other pathophysiological markers, cognitive status, and
demographic and genetic variables. Assessment of early/preclinical change will include examination of
Aβ striatal patterns and early detection of tau deposition in entorhinal cortex in the context of subsequent
detection of tau spread to cortical areas with disease progression. We will also evaluate the relationship
of Aβ and tau to other pathophysiological markers (e.g., MRI volumetric measures), to cognitive
performance and include covariates (e.g., age, education, and genetic risk factors), in consideration of
factors contributing to the biological and clinical heterogeneity in DS. This work will provide a more
comprehensive and personalized evaluation of the individual’s status. The analysis platform will be
shared to facilitate feasible multimodal analyses and promote novel multimodal science, multimodal
hypothesis development, and multidisciplinary ABC-DS collaboration. This research is highly relevant to
the goals and priorities of both the parent ABC-DS grant (U19 AG068054, “Alzheimer Biomarker
Consortium – Down Syndrome”) and the INCLUDE project.

## Key facts

- **NIH application ID:** 10670475
- **Project number:** 3U19AG068054-03S3
- **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:** $177,627
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670475

## Citation

> US National Institutes of Health, RePORTER application 10670475, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)-04 Supplement 4 (3U19AG068054-03S3). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10670475. Licensed CC0.

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