Evidence map›Paper›PMID 37842184›Full record

ArticleExtracellular vesicles and circulating nucleic acids2023

Synaptic proteins in neuron-derived extracellular vesicles as biomarkers for Alzheimer's disease: novel methodology and clinical proof of concept.

Erez Eitan, Tricia Thornton-Wells, Katya Elgart, Eren Erden, Eve Gershun, Amir Levine, Olga Volpert, Mitra Azadeh, Daniel G Smith, Dimitrios Kapogiannis

Open access · hybridAbstract read
In one paragraph

Article in Extracellular vesicles and circulating nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
10.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 69 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Extracellular Vesicles in Tauopathies: Mechanisms and Applications.International journal of molecular sciences · 2026
    Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Erez EitanNeuroDex Inc., Natick, MA 01760, USA.ORCID 0000-0001-6908-8352
Tricia Thornton-WellsAlkermes, Inc., Department of Translational Medicine and Early-Stage Clinical Development, Waltham, MA 02451-1420, USA.
Katya ElgartNeuroDex Inc., Natick, MA 01760, USA.
Eren ErdenNational Institute on Aging (NIA/NIH), Human Neuroscience Section, Intramural Research Program, Baltimore, MD 21224, USA.
Eve GershunNeuroDex Inc., Natick, MA 01760, USA.
Amir LevineColumbia University, Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Physicians and Surgeons, New York, NY 10032, USA.
Olga VolpertNeuroDex Inc., Natick, MA 01760, USA.
Mitra AzadehAlkermes, Inc., Department of Translational Medicine and Early-Stage Clinical Development, Waltham, MA 02451-1420, USA.
Daniel G SmithAlkermes, Inc., Department of Translational Medicine and Early-Stage Clinical Development, Waltham, MA 02451-1420, USA.
Dimitrios KapogiannisNational Institute on Aging (NIA/NIH), Human Neuroscience Section, Intramural Research Program, Baltimore, MD 21224, USA.ORCID 0000-0001-6908-8352
NeuroBioTex (United States) · USAlkermes (United States) · USColumbia University · USInstitute on Aging · USNational Institute on Aging · US

Funding

Studies in Dementia and Neurodegenerative DiseasesZIAAG000975 · NIA · NATIONAL INSTITUTE ON AGING · PI KAPOGIANNIS, DIMITRIOS · 2009 to 2025
$31.5M
Extraceullar Vesicle Biomarkers for Prediction of Cognitive Decline, Ab and TAU Accumulation, and atrophy in Preclinical Alzheimer's DiseaseZIAAG000003 · NIA · NATIONAL INSTITUTE ON AGING · PI KAPOGIANNIS, DIMITRIOS · 2022 to 2025
$4.4M
Intramural NIH HHS Z99 AG999999Intramural NIH HHS ZIA AG000003Intramural NIH HHS ZIA AG000975
6 · The paper itself

Abstract

Aims: Blood biomarkers can improve drug development for Alzheimer's disease (AD) and its treatment. Neuron-derived extracellular vesicles (NDEVs) in plasma offer a minimally invasive platform for developing novel biomarkers that may be used to monitor the diverse pathogenic processes involved in AD. However, NDEVs comprise only a minor fraction of circulating extracellular vesicles (EVs). Most published studies have leveraged the L1 cell adhesion molecule (L1CAM) for NDEV immunocapture. We aimed to develop and optimize an alternative, highly specific immunoaffinity method to enrich blood NDEVs for biomarker development. Methods: After screening multiple neuronal antigens, we achieved NDEV capture with high affinity and specificity using antibodies against Growth-Associated Protein (GAP) 43 and Neuroligin 3 (NLGN3). The EV identity of the captured material was confirmed by electron microscopy, western blotting, and proteomics. The specificity for neuronal origin was demonstrated by showing enrichment for neuronal markers (proteins, mRNA) and recovery of spiked neuronal EVs. We performed NDEV isolation retrospectively from plasma samples from two cohorts of early AD patients (N = 19 and N = 40) and controls (N = 20 and N = 19) and measured p181-Tau, amyloid-beta (Aβ) 42, brain-derived neurotrophic factor (BDNF), precursor brain-derived neurotrophic factor (proBDNF), glutamate receptor 2 (GluR2), postsynaptic density protein (PSD) 95, GAP43, and syntaxin-1. Results: p181-Tau, Aβ42, and NRGN were elevated in AD samples, whereas proBDNF, GluR2, PSD95, GAP43, and Syntaxin-1 were reduced. Differences for p181-Tau, proBDNF, and GluR2 survived multiple-comparison correction and were correlated with cognitive scores. A model incorporating biomarkers correctly classified 94.7% of AD participants and 61.5% of control participants. The observed differences in NDEVs-associated biomarkers are consistent with previous findings. Conclusion: NDEV isolation by GAP43 and NLGN3 immunocapture offers a robust novel platform for biomarker development in AD, suitable for large-scale validation.

Indexed as

Alzheimer’s diseaseBiomarkersexosomesneuron-derived exosomes

Identifiers

PMID37842184
PMCPMC10568955
OpenAlexW4361984009

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.