An acoustofluidic device for diagnosing preclinical Alzheimer's disease - Abstract
Alzheimer’s disease (AD) is a progressive, disabling neurodegenerative illness that affects an estimated
5.5 million people in the United States and approximately 10% of the population over the age of 65. Early
symptoms of the disease include short-term memory loss, difficulties with language, and mood swings;
however, symptoms gradually worsen over time, ultimately leading to dementia and a loss of bodily
functions. Significant challenges exist in the diagnosis of AD. In recent years, neuron-derived exosomes
(30-150 nm extracellular vesicles) have emerged as a promising biomarker for diagnosing AD. Neuron-
derived exosomes are an interesting target because they are able to cross the blood-brain barrier and they
contain markers that are specific to their cell of origin (i.e. neurons). As a result, neuron-derived exosomes
found in circulation can provide a simple, non-invasive means of monitoring the health of the central
nervous system. Accumulating evidence suggests that neuron-derived exosomes may play a crucial role
in the pathology of AD by helping to spread abnormal, potentially disease-causing, misfolded proteins
throughout the brain. Preliminary studies have shown that by analyzing the number of neuron-derived
exosomes and their molecular cargo (such as tau, amyloid-beta, and different microRNA levels), early-
stage AD patients can be distinguished from healthy controls, as well as patients with other neurological
diseases. While researchers have made progress in identifying neuron-derived exosomal proteins and
RNAs, difficulties surrounding the isolation and analysis of exosomes have prevented their widespread
use a biomarker for AD. Currently, there are no commercially available products capable of simultaneously
isolating and analyzing neuron-derived exosomes. In this SBIR Phase I project, we will address this unmet
need by demonstrating the feasibility and utility of an acoustofluidic (i.e. the fusion of acoustics and
microfluidics) platform for automated, high-purity, high-yield, biocompatible exosome isolation and
accurate exosome analysis for AD diagnosis. With its advantages in automation, speed, precision, and
accuracy, the proposed acoustofluidic technology has the potential to greatly simplify and revolutionize the
diagnosis of AD. If successful, our acoustofluidic platform could be used to help standardize exosomal
biomarker research and identify preclinical AD patients at early stages for future disease-altering therapies.
