% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Eninger:164654,
      author       = {Eninger, Timo and Müller, Stephan A. and Bacioglu, Mehtap
                      and Schweighauser, Manuel and Lambert, Marius and Maia, Luis
                      F. and Neher, Jonas and Hornfeck, Sarah M and Obermüller,
                      Ulrike and Kleinberger, Gernot and Haass, Christian and
                      Kahle, Philipp and Staufenbiel, Matthias and Ping, Lingyan
                      and Duong, Duc M. and Levey, Allan I. and Seyfried, Nicholas
                      T. and Lichtenthaler, Stefan and Jucker, Mathias and Kaeser,
                      Stephan A.},
      title        = {{S}ignatures of glial activity can be detected in the {CSF}
                      proteome},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {119},
      number       = {24},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DZNE-2022-01184},
      pages        = {e2119804119},
      year         = {2022},
      abstract     = {Single-cell transcriptomics has revealed specific glial
                      activation states associated with the pathogenesis of
                      neurodegenerative diseases, such as Alzheimer’s and
                      Parkinson’s disease. While these findings may eventually
                      lead to new therapeutic opportunities, little is known about
                      how these glial responses are reflected by biomarker changes
                      in bodily fluids. Such knowledge, however, appears crucial
                      for patient stratification, as well as monitoring disease
                      progression and treatment responses in clinical trials.
                      Here, we took advantage of well-described mouse models of
                      β-amyloidosis and α-synucleinopathy to explore
                      cerebrospinal fluid (CSF) proteome changes related to their
                      respective proteopathic lesions. Nontargeted liquid
                      chromatography-mass spectrometry revealed that the majority
                      of proteins that undergo age-related changes in CSF of
                      either mouse model were linked to microglia and astrocytes.
                      Specifically, we identified a panel of more than 20
                      glial-derived proteins that were increased in CSF of aged
                      β-amyloid precursor protein- and α-synuclein-transgenic
                      mice and largely overlap with previously described
                      disease-associated glial genes identified by single-cell
                      transcriptomics. Our results also show that enhanced
                      shedding is responsible for the increase of several of the
                      identified glial CSF proteins as exemplified for TREM2.
                      Notably, the vast majority of these proteins can also be
                      quantified in human CSF and reveal changes in Alzheimer’s
                      disease cohorts. The finding that cellular transcriptome
                      changes translate into corresponding changes of CSF proteins
                      is of clinical relevance, supporting efforts to identify
                      fluid biomarkers that reflect the various functional states
                      of glial responses in cerebral proteopathies, such as
                      Alzheimer’s and Parkinson’s disease.},
      keywords     = {Alzheimer Disease: cerebrospinal fluid / Alzheimer Disease:
                      metabolism / Animals / Biomarkers: cerebrospinal fluid /
                      Cerebrospinal Fluid: metabolism / Gene Expression Profiling
                      / Humans / Mice / Neuroglia: metabolism / Parkinson Disease:
                      cerebrospinal fluid / Parkinson Disease: metabolism /
                      Proteome: metabolism / Single-Cell Analysis / tau Proteins},
      cin          = {AG Jucker / AG Lichtenthaler / AG Neher / AG Herms / AG
                      Haass / AG Kahle / Ext UKT},
      ddc          = {500},
      cid          = {I:(DE-2719)1210001 / I:(DE-2719)1110006 /
                      I:(DE-2719)1210012 / I:(DE-2719)1110001 / I:(DE-2719)1110007
                      / I:(DE-2719)1210000-4 / I:(DE-2719)5000058},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9214531},
      pubmed       = {pmid:35666874},
      doi          = {10.1073/pnas.2119804119},
      url          = {https://pub.dzne.de/record/164654},
}