# AMP-AD Brain Proteomic Network Enhancement, Validation, and Translation into CSF Biomarkers

> **NIH NIH U01** · EMORY UNIVERSITY · 2020 · $271,410

## Abstract

Project Summary
There is an unmet need to develop novel therapeutic targets and biomarkers for Alzheimer's disease (AD) and
related disorders. During the first phase of consortium, we have added the unique dimension of discovery
proteomics to the Accelerating Medicines Partnership (AMP)-AD. We successfully established a high throughput
proteomics pipeline and quantified 2-3000 proteins by mass spectrometry (MS) in >1800 postmortem human
brains for all AMP-AD teams. Using systems biology tools, we identified highly conserved AD proteomic networks
that complement and extend transcriptomic networks, highlighting a set of protein co-expression modules
strongly associated with diagnosis, cognition, and neuropathology. Experimental validation of several novel
protein targets in these modules confirmed links to neurodegeneration in model systems and in human brain
pathology. The overall goal of this renewal application is to fill several key gaps in AMP-AD, which are to enrich
and validate the AD brain co-expression network (with coverage of >11,000 proteins, >30,000 phosphosites, and
interacting proteins), and better define optimal novel targets for the entire consortium. Using new MS
technologies and proven cross-species experimental strategies, we will provide high confidence of module
membership necessary to guide therapeutic and biomarker applications. We also will translate these targets into
actionable biomarkers to monitor these modules and the respective pathophysiologies in living subjects with the
following aims: 1) Integrate proteomics, phosphoproteomics and protein-protein interactions to extend AD
networks and define key signaling and pathophysiological pathways linked to AMP-AD targets; 2) Validate
predicted network structure for the most promising AMP-AD targets in experimental model systems; and 3)
Translate the list of nominated AMP-AD targets including key trait-associated modules and hub proteins into
novel CSF biomarkers for AD. The results will amplify the impact of the AMP-AD with rapid and full data sharing
and establish an innovative pipeline for discovery and validation of brain proteomics targets and companion CSF
biomarkers that serve as robust and reproducible indicators of AD, including the dysregulated processes that
occur in brain.

## Key facts

- **NIH application ID:** 10116679
- **Project number:** 3U01AG061357-02S3
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** ALLAN I LEVEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $271,410
- **Award type:** 3
- **Project period:** 2018-09-30 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116679

## Citation

> US National Institutes of Health, RePORTER application 10116679, AMP-AD Brain Proteomic Network Enhancement, Validation, and Translation into CSF Biomarkers (3U01AG061357-02S3). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116679. Licensed CC0.

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