Ultrasound-Amplified Exosome Secretion and Antibody-Free SERS Profiling for APOE Genotype-Dependent Signatures

ABSTRACT: Exosomes offer a promising platform for non-invasive diagnosis of neurodegenerative diseases by encapsulating multiple biomarkers and crossing the blood–brain barrier. However, conventional exosome analyses often fail to capture subtle, genotype-specific pathological variations due to limited vesicle yield, low detection sensitivity, and reliance on predefined markers. Here, we present an integrated approach that combines ultrasound-induced exosome amplification with an antibody-free surface-enhanced Raman scattering (SERS) platform to sensitively detect genotype-dependent pathological differences. By applying optimized low-intensity pulsed ultrasound (LIPUS), we achieved up to 100-fold enhancement in exosome secretion via the endosomal sorting complexes required for transport (ESCRT) pathway and monitored the dynamics of this amplification. To improve detection, we developed a gold-coated zinc oxide (ZnO) nanowire-based SERS substrate that amplifies exosomal signal intensity by more than fourfold without requiring antibodies. Using multiplex SERS profiling of intact exosomes combined with principal component analysis (PCA), we successfully distinguished apolipoprotein E (APOE) genotypes, improving the silhouette score from 0.37 to 0.5. Consistently, transcriptome analysis substantiates these findings by showing that LIPUS stimulation increased exosome secretion and upregulated exosome-related genes functionally related to Alzheimer's disease (AD). These findings demonstrate that label-free, intact exosome profiling can reveal genotype-dependent pathological variations, supporting its potential utility in high-sensitivity precision diagnostics for AD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309078 | GEO | 2026/08/11

REPOSITORIES: GEO