Can Blood-Based Molecules Provide a Window Into Brain Disease?

Biomarker development in biomedical research requires years, progressing from initial exciting results to validation in expanding cohorts of more subjects and, finally, to rigorously tested markers that performed across institutions, Navneet Dogra, PhD, said in framing his research. A current research project addressed whether blood-based testing of extracellular vesicles (EVs) and related particles for Alzheimer disease detection could be made reproducible across institutions and technicians.

The project paired 2 laboratories: Dogra's and a collaborating laboratory at Harvard Medical School. Each followed the same protocol, isolated EVs from blood, and tested the samples independently. The 2 sets of results were then compared to determine which findings matched, which did not, and how discordant findings could be improved. The differences were intended to guide refinement of the isolation method. Rigorous, reproducible testing across institutions and technicians was framed as a step toward brain-based diagnosis.¹

The effort built on an earlier observation: approximately 5 to 6 years ago, a student in Dogra's laboratory isolated EVs from patient blood and recovered particles of heterogeneous sizes. Electron microscopy showed round, ball-like EVs alongside tiny electron-dense particles whose identity was initially unknown. EVs measured about 1000 times smaller than the thickness of a hair, and the electron-dense particles were about half the size of EVs. "We started looking at these particles and we found a set of brain specific RNA were enriched in these tiny particles," Dogra said.² The group named the particles SECmeres, a term derived from size exclusion chromatography.

Blood therefore contained at least 2 distinct populations— larger EVs and smaller SECmeres—that carried different sets of RNA. "We don't know how they are formed, what their function is, but we know they're carrying different set of RNA markers from brain," Dogra said. This particle heterogeneity represented a fundamentally exciting direction for the field, added Dogra.

Dr Dogra is an assistant professor at the Icahn School of Medicine at Mount Sinai.

References

1. Dogra N, Chen TY, Gonzalez-Kozlova E, et al. Extracellular vesicles carry transcriptional 'dark matter' revealing tissue-specific information. J Extracell Vesicles. 2024;13(8):e12481.

2. Gonzalez-Kozlova E, Tichkule S, Nose Y, et al. SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer's disease. Nat Commun. 2026;17(1):5453.