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

• Published in: Nature communications 2022-11, Vol.13 (1), p.7210-18, Article 7210
• Main Authors: Fernández Zapata, Camila, Giacomello, Ginevra, Spruth, Eike J., Middeldorp, Jinte, Gallaccio, Gerardina, Dehlinger, Adeline, Dames, Claudia, Leman, Julia K. H., van Dijk, Roland E., Meisel, Andreas, Schlickeiser, Stephan, Kunkel, Desiree, Hol, Elly M., Paul, Friedemann, Parr, Maria Kristina, Priller, Josef, Böttcher, Chotima
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/21; 13/31; 49; 49/79; 631/250/2504; 631/378/371; Alzheimer Disease - metabolism; Alzheimer's disease; Biomarkers; Biomarkers - metabolism; Blood; Brain; Cerebrospinal fluid; Choroid plexus; Choroid Plexus - metabolism; Compartments; Environmental changes; Humanities and Social Sciences; Humans; Immune system; Metabolism; multidisciplinary; Myeloid cells; Myeloid Cells - metabolism; Myeloid Progenitor Cells - metabolism; Neurodegenerative diseases; Parenchyma; Peripheral blood; Phagocytosis; Phenotype; Phenotypes; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34719-2

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. Multiple state-of-the-art analyses of immune cells in 117 blood, 117 cerebrospinal fluid, 13 choroid plexus and 13 brain parenchyma samples reveal differential characteristics of immune cells in different body compartments and different diseases.