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

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, Stephan Schlickeiser, Desiree Kunkel, Elly M Hol, Friedemann Paul, Maria Kristina Parr, Josef Priller, Chotima Böttcher

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)7210
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 23 Nov 2022

Keywords

  • Humans
  • Alzheimer Disease/metabolism
  • Choroid Plexus/metabolism
  • Myeloid Cells/metabolism
  • Myeloid Progenitor Cells/metabolism
  • Biomarkers/metabolism
  • Phenotype

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