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@ARTICLE{Nissen:157801,
      author       = {Nissen, Sara Konstantin and Ferreira, Sara Almeida and
                      Nielsen, Marlene Christina and Schulte, Claudia and
                      Shrivastava, Kalpana and Hennig, Dorle and Etzerodt, Anders
                      and Graversen, Jonas Heilskov and Berg, Daniela and
                      Maetzler, Walter and Panhelainen, Anne and Møller, Holger
                      Jon and Brockmann, Kathrin and Romero-Ramos, Marina},
      title        = {{S}oluble {CD}163 {C}hanges {I}ndicate {M}onocyte
                      {A}ssociation {W}ith {C}ognitive {D}eficits in {P}arkinson's
                      {D}isease.},
      journal      = {Movement disorders},
      volume       = {36},
      number       = {4},
      issn         = {1531-8257},
      address      = {New York, NY},
      publisher    = {Wiley},
      reportid     = {DZNE-2021-01258},
      pages        = {963 - 976},
      year         = {2021},
      abstract     = {Parkinson's disease (PD) is a neurodegenerative disorder
                      with a significant immune component, as demonstrated by
                      changes in immune biomarkers in patients' biofluids.
                      However, which specific cells are responsible for those
                      changes is unclear because most immune biomarkers can be
                      produced by various cell types.The aim of this study was to
                      explore monocyte involvement in PD.We investigated the
                      monocyte-specific biomarker sCD163, the soluble form of the
                      receptor CD163, in cerebrospinal fluid (CSF) and serum in
                      two experiments, and compared it with other biomarkers and
                      clinical data. Potential connections between CD163 and
                      alpha-synuclein were studied in vitro.CSF-sCD163 increased
                      in late-stage PD and correlated with the PD biomarkers
                      alpha-synuclein, Tau, and phosphorylated Tau, whereas it
                      inversely correlated with the patients' cognitive scores,
                      supporting monocyte involvement in neurodegeneration and
                      cognition in PD. Serum-sCD163 increased only in female
                      patients, suggesting a sex-distinctive monocyte response.
                      CSF-sCD163 also correlated with molecules associated with
                      adaptive and innate immune system activation and with immune
                      cell recruitment to the brain. Serum-sCD163 correlated with
                      proinflammatory cytokines and acute-phase proteins,
                      suggesting a relation to chronic systemic inflammation. Our
                      in vitro study showed that alpha-synuclein activates
                      macrophages and induces shedding of sCD163, which in turn
                      enhances alpha-synuclein uptake by myeloid cells,
                      potentially participating in its clearance.Our data present
                      sCD163 as a potential cognition-related biomarker in PD and
                      suggest a role for monocytes in both peripheral and brain
                      immune responses. This may be directly related to
                      alpha-synuclein's proinflammatory capacity but could also
                      have consequences for alpha-synuclein processing. © 2020
                      The Authors. Movement Disorders published by Wiley
                      Periodicals LLC on behalf of International Parkinson and
                      Movement Disorder Society.},
      keywords     = {Amyloid beta-Peptides / Antigens, CD / Antigens,
                      Differentiation, Myelomonocytic / Biomarkers / Cognition /
                      Female / Humans / Monocytes / Parkinson Disease:
                      complications / Peptide Fragments / Receptors, Cell Surface
                      / alpha-Synuclein / alpha-synuclein (Other) / biomarkers
                      (Other) / cognition (Other) / monocytes (Other) / sCD163
                      (Other) / Amyloid beta-Peptides (NLM Chemicals) / Antigens,
                      CD (NLM Chemicals) / Antigens, Differentiation,
                      Myelomonocytic (NLM Chemicals) / Biomarkers (NLM Chemicals)
                      / CD163 antigen (NLM Chemicals) / Peptide Fragments (NLM
                      Chemicals) / Receptors, Cell Surface (NLM Chemicals) /
                      alpha-Synuclein (NLM Chemicals)},
      cin          = {AG Gasser / AG Berg},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)5000055},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33332647},
      pmc          = {pmc:PMC8247308},
      doi          = {10.1002/mds.28424},
      url          = {https://pub.dzne.de/record/157801},
}