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

doi:10.1038/s41467-022-34719-2

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

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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 language	English
Article number	7210
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-34719-2
Publication status	Published - 23 Nov 2022

Keywords

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

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Fernández Zapata, C., Giacomello, G., Spruth, E. J., Middeldorp, J., Gallaccio, G., Dehlinger, A., Dames, C., Leman, J. K. H., van Dijk, R. E., Meisel, A., Schlickeiser, S., Kunkel, D., Hol, E. M., Paul, F., Parr, M. K., Priller, J., & Böttcher, C. (2022). Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer's disease. Nature Communications, 13(1), Article 7210. https://doi.org/10.1038/s41467-022-34719-2

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

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.",

keywords = "Alzheimer Disease/metabolism, Biomarkers/metabolism, Choroid Plexus/metabolism, Humans, Myeloid Cells/metabolism, Myeloid Progenitor Cells/metabolism, Phenotype",

author = "{Fern{\'a}ndez Zapata}, Camila and Ginevra Giacomello and Spruth, {Eike J} and Jinte Middeldorp and Gerardina Gallaccio and Adeline Dehlinger and Claudia Dames and Leman, {Julia K H} and {van Dijk}, {Roland E} and Andreas Meisel and Stephan Schlickeiser and Desiree Kunkel and Hol, {Elly M} and Friedemann Paul and Parr, {Maria Kristina} and Josef Priller and Chotima B{\"o}ttcher",

note = "Funding Information: We thank Jasmin Jamal El-Din and Christian B{\"o}ttcher for excellent technical assistance with sample collection and ex vivo experiments. We would also like to acknowledge the assistance of the Flow & Mass Cytometry Core Facility (BIH at Charit{\'e}—Universit{\"a}tsmedizin Berlin, Germany) and the Netherlands Brain Bank (Amsterdam, The Netherlands). G.Gi. was funded by the Elsa-Neumann scholarship of the State of Berlin. G.Gi. and G.Ga. received the PhD scholarship from the NeuroMac School (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05)). A.M. and C.D. were were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B12)), and the Leducq Foundation (19CVD01). R.E.v.D., J.M. and E.M.H. were funded by ZonMW 733050107. C.B. and J.P. were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05 and B07)). Funding Information: We thank Jasmin Jamal El-Din and Christian B{\"o}ttcher for excellent technical assistance with sample collection and ex vivo experiments. We would also like to acknowledge the assistance of the Flow & Mass Cytometry Core Facility (BIH at Charit{\'e}—Universit{\"a}tsmedizin Berlin, Germany) and the Netherlands Brain Bank (Amsterdam, The Netherlands). G.Gi. was funded by the Elsa-Neumann scholarship of the State of Berlin. G.Gi. and G.Ga. received the PhD scholarship from the NeuroMac School (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05)). A.M. and C.D. were were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B12)), and the Leducq Foundation (19CVD01). R.E.v.D., J.M. and E.M.H. were funded by ZonMW 733050107. C.B. and J.P. were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05 and B07)). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = nov,

day = "23",

doi = "10.1038/s41467-022-34719-2",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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Fernández Zapata, C, Giacomello, G, Spruth, EJ, Middeldorp, J, Gallaccio, G, Dehlinger, A, Dames, C, Leman, JKH, van Dijk, RE, Meisel, A, Schlickeiser, S, Kunkel, D, Hol, EM, Paul, F, Parr, MK, Priller, J & Böttcher, C 2022, 'Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer's disease', Nature Communications, vol. 13, no. 1, 7210. https://doi.org/10.1038/s41467-022-34719-2

TY - JOUR

T1 - Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer's disease

AU - Fernández Zapata, Camila

AU - Giacomello, Ginevra

AU - Spruth, Eike J

AU - Middeldorp, Jinte

AU - Gallaccio, Gerardina

AU - Dehlinger, Adeline

AU - Dames, Claudia

AU - Leman, Julia K H

AU - van Dijk, Roland E

AU - Meisel, Andreas

AU - Schlickeiser, Stephan

AU - Kunkel, Desiree

AU - Hol, Elly M

AU - Paul, Friedemann

AU - Parr, Maria Kristina

AU - Priller, Josef

AU - Böttcher, Chotima

N1 - Funding Information: We thank Jasmin Jamal El-Din and Christian Böttcher for excellent technical assistance with sample collection and ex vivo experiments. We would also like to acknowledge the assistance of the Flow & Mass Cytometry Core Facility (BIH at Charité—Universitätsmedizin Berlin, Germany) and the Netherlands Brain Bank (Amsterdam, The Netherlands). G.Gi. was funded by the Elsa-Neumann scholarship of the State of Berlin. G.Gi. and G.Ga. received the PhD scholarship from the NeuroMac School (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05)). A.M. and C.D. were were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B12)), and the Leducq Foundation (19CVD01). R.E.v.D., J.M. and E.M.H. were funded by ZonMW 733050107. C.B. and J.P. were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05 and B07)). Funding Information: We thank Jasmin Jamal El-Din and Christian Böttcher for excellent technical assistance with sample collection and ex vivo experiments. We would also like to acknowledge the assistance of the Flow & Mass Cytometry Core Facility (BIH at Charité—Universitätsmedizin Berlin, Germany) and the Netherlands Brain Bank (Amsterdam, The Netherlands). G.Gi. was funded by the Elsa-Neumann scholarship of the State of Berlin. G.Gi. and G.Ga. received the PhD scholarship from the NeuroMac School (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05)). A.M. and C.D. were were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B12)), and the Leducq Foundation (19CVD01). R.E.v.D., J.M. and E.M.H. were funded by ZonMW 733050107. C.B. and J.P. were funded by the Deutsche Forschungsgemeinschaft (DFG, the German Research Foundation—Project-ID 259373024—CRC/TRR 167 (B05 and B07)). Publisher Copyright: © 2022, The Author(s).

PY - 2022/11/23

Y1 - 2022/11/23

N2 - 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.

AB - 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.

KW - Alzheimer Disease/metabolism

KW - Biomarkers/metabolism

KW - Choroid Plexus/metabolism

KW - Humans

KW - Myeloid Cells/metabolism

KW - Myeloid Progenitor Cells/metabolism

KW - Phenotype

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U2 - 10.1038/s41467-022-34719-2

DO - 10.1038/s41467-022-34719-2

M3 - Article

C2 - 36418303

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7210

ER -

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

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