# Peptide Biomarkers for Alzheimer Disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $703,753

## Abstract

Summary
Significant progress has been made in using neuroimaging and cerebrospinal fluid (CSF) protein
measurements as Alzheimer disease (AD) biomarkers. However, there is still a critical need to
identify more reliable and reproducible biomarkers with further improved diagnostic accuracy,
especially to differentiate AD from other dementias, to track or monitor the disease progression
and to objectively evaluate drug effects. There is also a growing interest in developing novel
biomarkers that could reflect different aspects of AD pathology and accurately detect pathogenic
components of AD before appearance of significant cognitive decline, thereby assisting with AD
diagnosis at early symptomatic and even preclinical stages. This proposal is designed to meet
several major challenges of current biomarker research, specifically: 1) difficulties in development
of antibody-based, quantitative protein assays for most novel candidates identified by proteomic
profiling and significant variations associated with most existing immunoassays, 2) low sensitivity
and specificity of blood-based markers, and 3) detection of AD at early or even preclinical stages.
To address the problems of antibody-based assays, our strategy is development of targeted mass
spectrometry-based techniques, such as selected reaction monitoring (SRM), to identify unique
peptide markers derived from proteins either showing promise in previous proteomics profiling, or
known to be critical to AD pathogenesis in human cerebrospinal fluid (CSF). To facilitate discovery
and validation of blood based biomarkers, a specific population of central nervous system derived
plasma exosomes, the cargo-carrying microvesicles recognized recently to transport biomolecules
among different cells or organ systems, will be isolated before SRM analysis. The unique peptide
markers will be tested in several large, well-established cohorts, e.g., Alzheimer's Disease
Research Centers (ADRCs) affiliated with the University of Washington, Oregon Health and
Science University, University of California at San Diego, and University of Pennsylvania, and
ADNI (Alzheimer's Disease Neuroimaging Initiative), with cross-sectional and longitudinal samples
collected, along with extensive clinical characterization. Finally, to improve early diagnosis, we will
make use of a very early MCI cohort consisting of subjects at elevated risk for AD, with the goal of
discovering biomarkers capable of identifying subjects with early or preclinical AD. The studies
designed for this project, if successful, have the potential to result in a panel(s) of biomarkers that
are robust, with less variation than can currently be achieved, and in a body fluid that is readily
accessible in a regular clinical setting. Markers for early diagnosis and progression of AD are critical
in understanding how to arrest or slow AD progression.

## Key facts

- **NIH application ID:** 10183119
- **Project number:** 5R01AG056711-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Min Shi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $703,753
- **Award type:** 5
- **Project period:** 2017-08-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183119

## Citation

> US National Institutes of Health, RePORTER application 10183119, Peptide Biomarkers for Alzheimer Disease (5R01AG056711-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10183119. Licensed CC0.

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