Evidence map›Paper›PMID 40210837›Full record

ArticleMolecular neurobiology2025

Most L1CAM Is not Associated with Extracellular Vesicles in Human Biofluids and iPSC-Derived Neurons.

Vaibhavi Kadam, Madeleine Wacker, Patrick Oeckl, Milena Korneck, Benjamin Dannenmann, Julia Skokowa, Stefan Hauser, Markus Otto, Matthis Synofzik, David Mengel

Abstract read
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

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  16. ICAM-5: A Novel Marker for Neuronally Derived Extracellular Vesicles.bioRxiv : the preprint server for biology · 2025
    Article
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  18. 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.

Vaibhavi KadamDivision Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tuebingen, Tuebingen, Germany.
Madeleine WackerDivision Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tuebingen, Tuebingen, Germany.
Patrick OecklDepartment of Neurology, Ulm University Hospital, Ulm, Germany.
Milena KorneckGerman Center for Neurodegenerative Diseases (DZNE) Tuebingen, Tuebingen, Germany.
Benjamin DannenmannDepartment of Oncology, Hematology, Immunology, and Rheumatology, University Hospital Tuebingen, Tuebingen, Germany.
Julia SkokowaDepartment of Oncology, Hematology, Immunology, and Rheumatology, University Hospital Tuebingen, Tuebingen, Germany.
Stefan HauserGerman Center for Neurodegenerative Diseases (DZNE) Tuebingen, Tuebingen, Germany.
Markus OttoDepartment of Neurology, Ulm University Hospital, Ulm, Germany.
Matthis Synofzik *Division Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tuebingen, Tuebingen, Germany. matthis.synofzik@uni-tuebingen.de.
David Mengel *Division Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tuebingen, Tuebingen, Germany. david.mengel@uni-tuebingen.de.

Funding

Baden-Württemberg Stiftung 1.16101.21EU Joint Programme - Neurodegenerative Disease Research 2019-02248Medizinischen Fakultät, Eberhard Karls Universität Tübingen 459-0-0
6 · The paper itself

Abstract

Transmembrane L1 cell adhesion molecule (L1CAM) is widely used as a marker to enrich for neuron-derived extracellular vesicles (EVs), especially in plasma. However, this approach lacks sufficient robust validation. This study aimed to assess whether human biofluids are indeed enriched for EVs, particularly neuron-derived EVs, by L1CAM immunoaffinity, utilizing multiple sources (plasma, CSF, conditioned media from iPSC-derived neurons [iNCM]) and different methods (mass spectrometry [MS], nanoparticle tracking analysis [NTA]). Following a systematic multi-step validation approach, we confirmed isolation of generic EV populations using size-exclusion chromatography (SEC) and polymer-aided precipitation (PPT)-two most commonly applied EV isolation methods-from all sources. Neurofilament light (NfL) was detected in both CSF and blood-derived EVs, indicating their neuronal origin. However, L1CAM immunoprecipitation did not yield enrichment of L1CAM in EV fractions. Instead, it was predominantly found in its free-floating form. Additionally, MS-based proteomic analysis of CSF-derived EVs also did not show L1CAM enrichment. Our study validates EV isolation from diverse biofluid sources by several isolation approaches and confirms that some EV subpopulations in human biofluids are of neuronal origin. Thorough testing across multiple sources by different orthogonal methods, however, does not support L1CAM as a marker to reliably enrich for a specific subpopulation of EVs, particularly of neuronal origin.

Indexed as

Body FluidsExtracellular VesiclesInduced Pluripotent Stem CellsNeural Cell Adhesion Molecule L1NeuronsHumansProteomicsL1CAM protein, humanNeural Cell Adhesion Molecule L1BiomarkersBloodCerebrospinal fluidExtracellular vesiclesImmunoprecipitationIsolation methodsL1CAMNeuron

Identifiers

PMID40210837
PMCPMC12289729

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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.