Exosome RNA Exosome RNA Research & Industry News
Researchers are actively searching for better ways to diagnose Alzheimer’s disease without relying on invasive procedures or expensive brain imaging. One promising approach is the use of liquid biopsies, which analyze molecules circulating in the blood. Among the most studied components are extracellular vesicles (EVs), tiny particles released by cells that carry proteins and RNA reflecting their tissue of origin.
A team led by researchers at the Icahn School of Medicine at Mount Sinai have discovered a previously unrecognized group of extremely small extracellular particles that may provide even better information about Alzheimer’s disease than conventional extracellular vesicles. The researchers named these particles SECmeres.
An overview of the study and findings
A Several brain-derived EVPs cross the blood brain barrier and reach circulation. B Different EVPs enrich different RNA cargo. The EVP-RNA is impacted, upregulated (green) or downregulated (red) in AD.
SECmeres are smaller than 50 nanometers and lack many of the characteristics associated with exosomes, exomeres, supermeres, and other known extracellular particles. Despite their small size, they contain RNA molecules and proteins that appear to originate from the brain.
The researchers compared blood samples from individuals with Alzheimer’s disease and healthy controls. They found that RNA signatures associated with SECmeres distinguished Alzheimer’s cases more effectively than RNA found in small extracellular vesicles. Large EVs, in contrast, showed little difference between the two groups.
Different RNA markers were enriched in different particle populations. Small EVs contained markers such as synaptotagmin, alpha-synuclein, and MAPT, while SECmeres contained molecules including L1CAM, syntaxin, and neurogranin. These findings suggest that multiple extracellular particle populations carry distinct information about brain health.
Using single-cell RNA sequencing deconvolution, the investigators examined the cellular origins of these RNA signatures. They found that small EVs contained transcripts from many different brain cell types, while SECmeres were enriched with transcripts originating from brain endothelial cells. These cells line blood vessels and form the blood-brain barrier, which plays an important role in maintaining brain function.
The findings challenge the current assumption that extracellular vesicles are the primary carriers of useful biomarkers in blood. Instead, SECmeres may represent a previously overlooked source of brain-derived information that could improve liquid biopsy approaches for Alzheimer’s disease.
Although larger clinical studies are still needed, these results suggest that analyzing different extracellular particles could eventually lead to more sensitive and accurate blood tests for neurodegenerative disorders.
