Researchers have identified a new class of blood nanoparticles that may improve the early diagnosis of Alzheimer’s disease, potentially outperforming the extracellular vesicles that have been the focus of most blood biomarker research to date.
The study, published in Nature Communications, describes previously unrecognized particles, termed "SECmeres," that carry brain-derived RNA signatures capable of distinguishing people with Alzheimer’s disease from cognitively normal controls. The findings suggest that future blood tests could become more sensitive by targeting these particles rather than relying solely on conventional extracellular vesicles.
Current laboratory diagnosis of Alzheimer’s disease increasingly relies on blood biomarkers measuring proteins such as amyloid-beta and phosphorylated tau. However, RNA-based biomarkers could provide complementary information by reflecting changes in multiple brain cell types and disease pathways. The investigators argue that SECmeres represent an overlooked source of diagnostic information because their small size means they are often discarded during standard extracellular vesicle isolation procedures.
Using blood and brain samples from 26 individuals with neuropathologically confirmed Alzheimer’s disease or no evidence of the disease, the researchers compared three classes of extracellular particles. Only the smaller extracellular vesicles and SECmeres consistently distinguished Alzheimer’s disease from controls, while larger vesicles showed no meaningful diagnostic value. SECmeres produced the strongest statistical discrimination and contained a distinct set of brain-derived RNA markers, including L1CAM, neurogranin, syntaxin, myelin basic protein, and ENO2. Small extracellular vesicles carried a different RNA profile, suggesting that each particle type captures different aspects of disease biology.
The study also introduces a laboratory workflow called SECrifuge, which combines size-exclusion chromatography, centrifugation, and filtration to isolate the particles in approximately 60 minutes using standard laboratory equipment. The authors report that the method is more reproducible than ultracentrifugation, requires no specialist instrumentation, and costs less than US$10 per preparation – features that could make it more practical for clinical laboratory adoption if validated.
For diagnostic laboratories, the principal implication is not the immediate introduction of a new Alzheimer’s test but a potential change in where biomarkers are sought. Rather than focusing exclusively on conventional extracellular vesicles, future assay development may need to include SECmeres to capture a broader range of disease-associated RNA signals.
The authors emphasize that the work is a proof-of-concept study. The cohort was relatively small, consisted primarily of White participants, and relied on samples collected after death. Larger prospective studies using blood samples from living patients, including those with mild cognitive impairment or early-stage Alzheimer’s disease, will be needed before the approach can be translated into routine clinical diagnostics.
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