SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer's disease.
Overview
13 affiliations
- Department of Immunology, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Department of Urology, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Department of Biochemistry and Neurology, Emory University,Atlanta, GA USA
- Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Department of Neurology, Yale University,New Haven, CT USA
- Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center,Bronx, NY USA
- Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center,Bronx, NY USA
- Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai,New York, NY USA
- Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai,New York, NY USA
Abstract
Cells release heterogeneous extracellular vesicles and particles (EVPs) into circulation, carrying RNA and proteins that reflect their origin. Recently, brain-derived EVs have gained significant attention as non-invasive biomarkers for Alzheimer’s disease (AD). Here, we identified sub-50nm extracellular nanoparticles in human brain and blood that lack the hallmarks of small EVs, exosomes, exomeres, and supermeres but are enriched for brain-specific markers, hereafter termed small EPs or ‘SECmeres’. We discovered that RNAs associated with SECmeres discriminated AD cases from controls with higher significance than small EVs, large EVs showed no differences. Discriminating RNAs were enriched in small EVs (Synaptotagmin, Alpha-synuclein, MAPT) or SECmeres (L1CAM, Syntaxin, Neurogranin), indicating distinct brain-derived signatures. Single-cell RNAseq deconvolution shows small EVs contain RNAs from diverse brain cells, whereas SECmeres enrich brain endothelial transcripts, lining cerebral blood vessels and forming the blood–brain barrier (BBB). These findings challenge the prevailing view that small EVs are the primary carriers of biomarkers. Collectively, our study shows that blood EVPs carry brain-specific information for liquid biopsy, pending validation in larger blinded clinical trials.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
No file of the authors' code could be read here: it is described below, and read at its source.
eegk/EVP-RNA-outperforms-extracellular-vesicles-as-blood-biomarkers-for-Alzheimer-disease
Availability: 1 check, the latest on 27 September 2026: the link is dead
- 27 September 2026: the link is dead
Code availability
This paper does not report original code. The code used is available on https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 0 scripts, each with its path and the digest of its content;
- no match between paragraphs and code yet;
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
Datasets cited
- zenodo:20073415, at Zenodo; found in “Data availability”
Data availability
Data reported in this paper has been shared with the manuscript by the lead contact. Transcriptomics and Proteomics data is available at 10.5281/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 21 authors, 1 keyword, 11 MeSH terms, 1 funder, 80 references.
Cite
This paper
Gonzalez-Kozlova, E., Tichkule, S., Nose, Y., Chen, T.-Y., Reznik, E., Santiago, J. V., Korrapati, A., Soleymani, T., Kosoy, R., Figueiredo, I., Lee, D., Hoffman, G. E., Kyprianou, N., Gordon, R. E., Cordon-Cardo, C., Rangaraju, S., Seyfried, N. T., Haroutunian, V., Fullard, J. F., . . . Dogra, N. (2026). SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer's disease. Nature communications, 17(1), 5453. https://
BibTeX
@article{gonzalezkozlova
author = {Gonzalez-Kozlova, Edgar and Tichkule, Swapnil and Nose, Yohei and Chen, Tzu-Yi and Reznik, Eduard and Santiago, Juliet V. and Korrapati, Anish and Soleymani, Taliah and Kosoy, Roman and Figueiredo, Igor and Lee, Donghoon and Hoffman, Gabriel E. and Kyprianou, Natasha and Gordon, Ronald E. and Cordon-Cardo, Carlos and Rangaraju, Srikant and Seyfried, Nicholas T. and Haroutunian, Vahram and Fullard, John F. and Roussos, Panos and Dogra, Navneet},
title = {{SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer's disease}},
journal = {Nature communications},
year = {2026},
month = jun,
volume = {17},
number = {1},
pages = {5453},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/
url = {https://
pmid = {42331820},
pmcid = {PMC13287576}
}
RIS
TY - JOUR
AU - Gonzalez-Kozlova, Edgar
AU - Tichkule, Swapnil
AU - Nose, Yohei
AU - Chen, Tzu-Yi
AU - Reznik, Eduard
AU - Santiago, Juliet V.
AU - Korrapati, Anish
AU - Soleymani, Taliah
AU - Kosoy, Roman
AU - Figueiredo, Igor
AU - Lee, Donghoon
AU - Hoffman, Gabriel E.
AU - Kyprianou, Natasha
AU - Gordon, Ronald E.
AU - Cordon-Cardo, Carlos
AU - Rangaraju, Srikant
AU - Seyfried, Nicholas T.
AU - Haroutunian, Vahram
AU - Fullard, John F.
AU - Roussos, Panos
AU - Dogra, Navneet
TI - SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer's disease
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/
VL - 17
IS - 1
SP - 5453
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1038/
"type": "article-journal",
"title": "SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer's disease",
"container-title": "Nature communications",
"author": [
{
"family": "Gonzalez-Kozlova",
"given": "Edgar"
},
{
"family": "Tichkule",
"given": "Swapnil"
},
{
"family": "Nose",
"given": "Yohei"
},
{
"family": "Chen",
"given": "Tzu-Yi"
},
{
"family": "Reznik",
"given": "Eduard"
},
{
"family": "Santiago",
"given": "Juliet V."
},
{
"family": "Korrapati",
"given": "Anish"
},
{
"family": "Soleymani",
"given": "Taliah"
},
{
"family": "Kosoy",
"given": "Roman"
},
{
"family": "Figueiredo",
"given": "Igor"
},
{
"family": "Lee",
"given": "Donghoon"
},
{
"family": "Hoffman",
"given": "Gabriel E."
},
{
"family": "Kyprianou",
"given": "Natasha"
},
{
"family": "Gordon",
"given": "Ronald E."
},
{
"family": "Cordon-Cardo",
"given": "Carlos"
},
{
"family": "Rangaraju",
"given": "Srikant"
},
{
"family": "Seyfried",
"given": "Nicholas T."
},
{
"family": "Haroutunian",
"given": "Vahram"
},
{
"family": "Fullard",
"given": "John F."
},
{
"family": "Roussos",
"given": "Panos"
},
{
"family": "Dogra",
"given": "Navneet"
}
],
"container-title-short":
"volume": "17",
"issue": "1",
"page": "5453",
"DOI": "10.1038/
"PMID": "42331820",
"PMCID": "PMC13287576",
"ISSN": "2041-1723",
"publisher": "Nature Publishing Group",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
6,
22
]
]
}
}
The tracing map gets a citation of its own once an author has validated it and it has a DOI.
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1038/s41467-026-75722-1 [code]
- Single-nucleus analysis of the adult human olfactory epithelium uncovers shared neurogenesis programs with the brain.Journal: Nature communicationsIn common: 1 reference, 2 authors
- [2] doi:10.1038/s41467-026-71281-7 [code]
- Downregulated transcription in chromosomal domains of midbrain dopamine neurons linked to schizophrenia.Journal: Nature communicationsIn common: 1 reference, 2 authors
- [3] doi:10.1038/s42003-026-10030-4 [code]
- Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.Journal: Communications biologyIn common: Alzheimer's / dementia, 1 reference, author Nicholas T. Seyfried
- [4] doi:10.1007/s00401-026-03042-1
- Tau368 improves p-tau diagnostic accuracy for FTLD-tau from FTLD-TDP.Journal: Acta neuropathologicaIn common: Alzheimer's / dementia, 3 references
- [5] doi:10.1038/s41467-026-70469-1
- Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice.Journal: Nature communicationsIn common: 3 references
- [6] doi:10.1002/alz.71273 [code]
- Proteomic profiling of brain organoids and extracellular vesicles identifies early Alzheimer's disease biomarkers and drug response heterogeneity.Journal: Alzheimer's & dementia : the journal of the Alzheimer's AssociationIn common: Alzheimer's / dementia, 2 references
- [7] doi:10.1038/s44328-026-00086-x [code]
- Microfluidic nanomagnetically isolated neuron- and astrocyte-derived extracellular vesicles to differentiate Lewy body and Alzheimer's disease.Journal: Npj biosensingIn common: Alzheimer's / dementia, 2 references
- [8] doi:10.1093/braincomms/fcag277
- Distinct brain extracellular vesicle microRNA profiles differ in frontotemporal dementia and Alzheimer's disease.Journal: Brain communicationsIn common: Alzheimer's / dementia, 2 references
- [9] doi:10.1002/alz.71773 [code]
- Brain-derived plasma p-tau217 shows enhanced dynamic range for Alzheimer's disease neuropathological change.Journal: Alzheimer's & dementia : the journal of the Alzheimer's AssociationIn common: Alzheimer's / dementia, 2 references
- [10] doi:10.1038/s42003-026-10525-0
- Efficient and specific selection of high-affinity DNA aptamers targeting μ-opioid receptor via functional extracellular vesicles.Journal: Communications biologyIn common: 2 references
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Validate its tracing map
You validate the map as this page shows it: 1 repository of the authors' code, each at its verified commit and with its license, 0 scripts, and 0 matches between paragraphs and code (see the Code and Map sections). It then receives a DOI on Zenodo, with you (your ORCID iD) and OSCR as its creators; the code itself is not deposited.
The map's fingerprint: sha256:c2dc76e283165b7b…
Add the badge to its README
The badge links the code to this page. Copy one of these into the README of the paper's code: only you decide where it goes, and nothing is changed for you.
Markdown
[, paste the snippet at the top, then “Commit changes…” and, to review it first, “Create a new branch and start a pull request”. You open the pull request; OSCR asks for no permission.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.