Abstract
INTRODUCTION
Accurate testing for Alzheimer’s disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.
METHODS
We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.
RESULTS
Circulating amyloid beta (Aβ), tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, p-tauS235, ubiquitin, and lysosomal-associated membrane protein 1–positive EVs distinguished AD samples. p-tau181, p-tau217, p-tauS235, and ubiquitin-positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p-tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p-tauS235.
DISCUSSION
This nFC-based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC-based measurements in larger populations and comparison to “gold standard” biomarkers is an exciting next step for developing AD diagnostic tools.
HIGHLIGHTS
Extracellular vesicles represent promising biomarkers of Alzheimer’s disease (AD) that can be measured in the peripheral circulation.
This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples.
Multiple markers including amyloid beta, tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, and p-tauS235 accurately distinguished AD samples from healthy controls.
Future studies should expand blood and cerebrospinal fluid–based EV biomarker development using nanoflow cytometry approaches.
If you do not see content above, kindly GO TO SOURCE.
Not all publishers encode content in a way that enables republishing at Neuro.vip.
This post is Copyright: Thamara Dayarathna,
Austyn D. Roseborough,
Janice Gomes,
Reza Khazaee,
Carolina R. A. Silveira,
Kathy Borron,
Soojung Yu,
Kristy Coleman,
Sarah Jesso,
Elizabeth Finger,
Penny MacDonald,
Michael Borrie,
Jennie Wells,
Robert Bartha,
Guangyong Zou,
Shawn N. Whitehead,
Hon S. Leong,
Stephen H. Pasternak | July 3, 2024