Developing EV surface proteins as biosignatures for Alzheimer's disease (AD)

PROJECT SUMMARY
The rising number of Americans currently living with Alzheimer’s disease (AD) demands pressing
therapeutic and diagnostic solutions. The consensus is that early detection is critical to delay and
better manage the disease. The recent discovery of extracellular vesicles (EVs) and their potentially
important cellular functions in neuronal-glial communication, synaptic plasticity, or as
endocannabinoid carriers has presented them as intriguing sources for neuronal disease diagnosis
and therapeutics. The growing body of functional studies have provided strong evidence that
EV-based disease markers, such as active miRNAs and signaling molecules, can be identified well
before the onset of symptoms or physiological detection of diseases, making them a promising
source for early-stage AD detection. However, multiple technical challenges related to EV-based
biomarker discovery have greatly limited its applications in clinical studies. In this STTR study that
focuses on innovative EV research and detection for AD, we will apply a novel strategy for EV
isolation and analysis, rigorously characterize disease-relevant EV surface proteins, and then focus
on developing EV surface proteins as biosignatures for AD. EV surface proteins, consisting of
receptors, transporters, channels, and enzymes, are a source of potential diagnostic biomarkers of
disease and therapeutic targets. More importantly, the detection of EV surface proteins can be
achieved in situ without long sample preparation procedure such as lysis, protein extraction,
digestion, enrichment and so on. The proposed strategy introduces a novel platform technology for
EV isolation and on-bead detection of EV surface proteins specific to AD. Accordingly, the following
aims will be completed: Aim #1: Implementation of an integrated strategy for fast and effective EV
isolation and cargo extraction; Aim #2: Characterization of EV surface proteins linked to AD; Aim #3:
Development of on-bead detection of EV surface proteins as biosignatures for AD. By the completion
of this exploratory project, we expect to establish a platform technology to detect EV surface proteins
as promising AD biomarkers for further validation.PROJECT NARRATIVE
There are many challenges how to tackle the Alzheimer’s disease (AD). This NIH STTR Phase I
project will attempt to develop an innovative platform technology that detect biosignatures based on
surface proteins in extracellular vesicles (EVs) isolated from blood and urine for AD early detection
and monitoring.