# Dissecting signaling pathways and seeking EV phosphoproteins as novel biomarkers for Alzheimer's Disease

> **NIH NIH RF1** · PURDUE UNIVERSITY · 2020 · $1,526,896

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disorder manifested by
cognitive and memory deterioration. The characteristic pathology changes in AD are fibrin
deposition in cerebral cortex, likely through the deposition of beta-amyloid (Aβ) in cell space and
hyperphosphorylated Tau protein in cell. However, the exact molecular mechanism and pathogenic
signaling of AD is not clear and researchers have been searching for new leads and reliable
diagnosis for AD. In this R01 study that focuses on innovative and translational AD research, we will
introduce novel strategies at the forefront of basic disease mechanism and clinical perspectives.
The long term goal of this project is 1) to develop systematic strategies to dissect kinase-substrate
signaling network related to onset of AD, with an emphasis on the identification and validation of
direct kinase-substrate relationship in AD’s critical pathogenic pathways; and 2) to develop
phosphorylated proteins in plasma extracellular vesicles (EVs) for potential clinical diagnosis. As
phosphorylation is a major player in early onset and progression of diseases such as AD, EV
phosphoproteins are expected to become actively pursued targets as indicators of cellular states
and for in vitro disease diagnosis. We will integrate novel proteomic approaches to identify Aβ and
Tau upstream kinases associated with the pathogenesis of AD and to dissect Aβ and Tau-
associated signaling networks. The strategy, fluorescence complementation mass spectrometry
(FCMS), will utilize protein complementation and quantitative proteomics to establish a high
throughput screening method to identify direct upstream kinases of Aβ and Tau associated with the
AD progression. Accordingly, we will achieve the following specific aims: 1): Understanding the
driving force of AD progression through the construction of high resolution kinase-substrate network
in Aβ and Tau associated signaling pathways; 2): Establishment of an analytical platform for
targeted detection of known AD biomarkers in plasma EVs; and 3): Discovery of phosphoproteins
from plasma EVs as novel biomarkers for AD detection and monitoring.

## Key facts

- **NIH application ID:** 10051758
- **Project number:** 1RF1AG064250-01A1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** W. Andy Tao
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,526,896
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051758

## Citation

> US National Institutes of Health, RePORTER application 10051758, Dissecting signaling pathways and seeking EV phosphoproteins as novel biomarkers for Alzheimer's Disease (1RF1AG064250-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051758. Licensed CC0.

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