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Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease

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  • Camila Fernández Zapata

    (a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Ginevra Giacomello

    (Freie Universität Berlin)

  • Eike J. Spruth

    (Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZNE)

  • Jinte Middeldorp

    (Utrecht University
    Biomedical Primate Research Centre)

  • Gerardina Gallaccio

    (a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Adeline Dehlinger

    (a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Claudia Dames

    (Charité-Universitätsmedizin Berlin)

  • Julia K. H. Leman

    (Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    Humboldt–Universität zu Berlin)

  • Roland E. van Dijk

    (Utrecht University)

  • Andreas Meisel

    (Charité-Universitätsmedizin Berlin
    Charité-Universitätsmedizin Berlin)

  • Stephan Schlickeiser

    (Institute of Medical Immunology, BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin)

  • Desiree Kunkel

    (Flow & Mass Cytometry Core Facility, Berlin Institute of Health at Charité - Universitätsmedizin Berlin)

  • Elly M. Hol

    (Utrecht University)

  • Friedemann Paul

    (a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    Charité-Universitätsmedizin Berlin
    Charité-Universitätsmedizin Berlin)

  • Maria Kristina Parr

    (Freie Universität Berlin)

  • Josef Priller

    (Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZNE
    Technical University Munich
    University of Edinburgh)

  • Chotima Böttcher

    (a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

Abstract

Myeloid cells are suggested as an important player in Alzheimer´s disease (AD). However, its continuum of phenotypic and functional changes across different body compartments and their use as a biomarker in AD remains elusive. Here, we perform multiple state-of-the-art analyses to phenotypically and metabolically characterize immune cells between peripheral blood (n = 117), cerebrospinal fluid (CSF, n = 117), choroid plexus (CP, n = 13) and brain parenchyma (n = 13). We find that CSF cells increase expression of markers involved in inflammation, phagocytosis, and metabolism. Changes in phenotype of myeloid cells from AD patients are more pronounced in CP and brain parenchyma and upon in vitro stimulation, suggesting that AD-myeloid cells are more vulnerable to environmental changes. Our findings underscore the importance of myeloid cells in AD and the detailed characterization across body compartments may serve as a resource for future studies focusing on the assessment of these cells as biomarkers in AD.

Suggested Citation

  • Camila Fernández Zapata & Ginevra Giacomello & Eike J. Spruth & Jinte Middeldorp & Gerardina Gallaccio & Adeline Dehlinger & Claudia Dames & Julia K. H. Leman & Roland E. van Dijk & Andreas Meisel & S, 2022. "Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34719-2
    DOI: 10.1038/s41467-022-34719-2
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    References listed on IDEAS

    as
    1. David Gate & Naresha Saligrama & Olivia Leventhal & Andrew C. Yang & Michael S. Unger & Jinte Middeldorp & Kelly Chen & Benoit Lehallier & Divya Channappa & Mark B. Los Santos & Alisha McBride & John , 2020. "Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease," Nature, Nature, vol. 577(7790), pages 399-404, January.
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