Key takeaways:

• Blood RNAs linked to brain-derived nanoparticles called SECmeres distinguished Alzheimer’s disease cases from controls.
• The discovery could provide a minimally invasive way for earlier diagnosis of Alzheimer’s.

The discovery of blood-based extracellular vesicles (EVs) and particles carrying brain-specific information could help make diagnoses for Alzheimer’s disease earlier and easier, according to research published in Nature Communications.

Navneet Dogra, MSc, PhD, assistant professor of pathology, molecular and cell-based medicine at the Icahn School of Medicine at Mount Sinai, said a brain affected by Alzheimer’s disease may release particles and RNA biomarkers that could be missed in testing that analyzes whole blood EVs for biomarkers. The research could make it possible to diagnose Alzheimer’s in real time with minimally invasive methods, such as liquid biopsies, he said.

Healio sat down with Dogra to learn more about his team’s research and what it means for the future of testing for and diagnosing Alzheimer’s disease.

Healio: How does your research build upon the current understanding of brain-derived extracellular vesicles (EVs) and their role in carrying biomarkers of Alzheimer’s disease?

Dogra: In 2025, FDA cleared the first protein-based blood test for Alzheimer’s disease diagnoses, which measures the p-tau217/beta-amyloid 1-42 ratio. A majority of the current research is focused on protein-based assays for Alzheimer’s disease. Our study demonstrates that blood extracellular vesicles and particles (EVPs) carry brain-specific RNA information that could be used for liquid biopsy approaches. We believe EVP-derived RNAs may reveal disease-related changes earlier in the disease process, before proteins or pathology become detectable.

In current clinical trial and commercial ventures, blood is considered as whole for biomarker discovery. We and others have found that there are heterogenous particles present in the blood, carrying unique proteins and RNAs. This discovery is important because Alzheimer’s disease brain may release different particles (SECmeres, large EVs, small EVs, lipoproteins, etc.) and RNAs based on disease pathogenesis, which could be missed in whole blood analysis.

While EVs have been shown to disseminate cargo between brain cells, SECmeres may have a new, unexplored function in Alzheimer’s disease brain biology.

Healio: When it comes to identifying biomarkers of Alzheimer’s, can you describe some of the key differences that came up in your work that differentiated SECmeres from large EVs and small EVs?

Dogra: We discovered that RNAs associated with SECmeres discriminated Alzheimer’s disease cases from controls with higher significance than small EVs. Large EVs showed no differences. Discriminating brain-specific RNAs were enriched in small EVs (synaptotagmin, alpha-synuclein, microtubule-associated protein tau) or SECmeres (L1 cell adhesion module, syntaxin, neurogranin), indicating distinct brain-derived signatures.

Healio: How do these biomarkers compare with other current biomarkers like p-tau217 , AB42/AB40 ratio and neurofilament light chain?

Dogra: In this study, we isolated and characterized EVP subpopulations (large EVs, small EVs and small EP) from postmortem brains and blood of neuropathologically confirmed Alzheimer’s disease and non-Alzheimer’s disease subjects, many of which had undergone apolipoprotein E genotype analysis, but their protein biomarkers data was not available. Our next step is to compare our RNA biomarkers with the current state of the art.

Healio: If validated, what impact might these biomarkers have on Alzheimer’s screening and diagnosis?

Dogra: Potentially, our SECmeres and EVs-based RNA biomarkers may lead to a PCR-based assay (similar to the COVID-19 test), which could be completed in a clinic visit. A longitudinal analysis may lead to projects of disease and response to therapy.

Healio: Is this research relevant when it comes to detecting other diseases beyond neurodegenerative disorders?

Dogra: Yes, this study could be applied beyond neurodegenerative disorders. We are currently exploring SECmeres in other diseases, including cancer, and we did find that some tissue-specific RNAs are enriched in SECmeres but not in the large and small EVs. This could mean that SECmeres can be particles of choice for some disease diagnosis.

Healio: Is your group at Mount Sinai continuing this research? If so, what are the next steps for validating what you’ve seen so far?

Dogra: Yes, we plan to expand this research and to conduct a validation in larger blinded clinical trials. We are also exploring SECmeres as biomarkers in prostate cancer.

For more information:

Navneet Dogra, MSc, PhD can be reached at NewsMedia@mssm.edu.