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@ARTICLE{Kadam:280113,
      author       = {Kadam, Vaibhavi and Wacker, Madeleine and Oeckl, Patrick
                      and Korneck, Milena and Dannenmann, Benjamin and Skokowa,
                      Julia and Hauser, Stefan and Otto, Markus and Synofzik,
                      Matthis and Mengel, David},
      title        = {{M}ost {L}1{CAM} {I}s not {A}ssociated with {E}xtracellular
                      {V}esicles in {H}uman {B}iofluids and i{PSC}-{D}erived
                      {N}eurons.},
      journal      = {Molecular neurobiology},
      volume       = {62},
      number       = {8},
      issn         = {0893-7648},
      address      = {Totowa, NJ},
      publisher    = {Humana Press},
      reportid     = {DZNE-2025-00896},
      pages        = {10427 - 10442},
      year         = {2025},
      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.},
      keywords     = {Humans / Extracellular Vesicles: metabolism / Neural Cell
                      Adhesion Molecule L1: metabolism / Neurons: metabolism /
                      Induced Pluripotent Stem Cells: metabolism / Induced
                      Pluripotent Stem Cells: cytology / Proteomics / Body Fluids:
                      metabolism / Biomarkers (Other) / Blood (Other) /
                      Cerebrospinal fluid (Other) / Extracellular vesicles (Other)
                      / Immunoprecipitation (Other) / Isolation methods (Other) /
                      L1CAM (Other) / Neuron (Other) / Neural Cell Adhesion
                      Molecule L1 (NLM Chemicals) / L1CAM protein, human (NLM
                      Chemicals)},
      cin          = {AG Gasser / AG Öckl / AG Hauser},
      ddc          = {570},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)5000073 /
                      I:(DE-2719)1210016},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40210837},
      doi          = {10.1007/s12035-025-04909-2},
      url          = {https://pub.dzne.de/record/280113},
}