Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
03 Jul 2024
Historique:
received: 15 09 2023
accepted: 11 06 2024
medline: 4 7 2024
pubmed: 4 7 2024
entrez: 3 7 2024
Statut: aheadofprint

Résumé

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment. This phenotype is defined by increased interleukin (IL)-17 and IL-1 coexpressed gene modules in blood neutrophils and in microglia of cognitively impaired female APOE ε4 carriers, showing increased infiltration to the AD brain. APOE4 female IL-17

Identifiants

DOI: 10.1038/s41591-024-03122-3 PMID: 38961225
pubmed: 38961225
doi: 10.1038/s41591-024-03122-3
pii: 10.1038/s41591-024-03122-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Cure Alzheimer's Fund (Alzheimer's Disease Research Foundation)
ID : 2022A005899
Organisme : BrightFocus Foundation (BrightFocus)
ID : 2020A016806
Organisme : Alzheimer's Association
ID : AARF-21-846786
Pays : United States

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Neta Rosenzweig (N)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-8668-6466

Kilian L Kleemann (KL)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.

Thomas Rust (T)

Department of Biomedical Sciences, Section Molecular Neurobiology, University Medical Center Groningen, Groningen, The Netherlands.
ORCID: 0000-0003-2000-8141

Madison Carpenter (M)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Madeline Grucci (M)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Michael Aronchik (M)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Nieske Brouwer (N)

Department of Biomedical Sciences, Section Molecular Neurobiology, University Medical Center Groningen, Groningen, The Netherlands.

Isabel Valenbreder (I)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0009-0006-9583-9520

Joya Cooper-Hohn (J)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Malvika Iyer (M)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Rajesh K Krishnan (RK)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Kisha N Sivanathan (KN)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Wesley Brandão (W)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Taha Yahya (T)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Ana Durao (A)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Zhuoran Yin (Z)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Jean Paul Chadarevian (JP)

Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.

Michael J Properzi (MJ)

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Roni Nowarski (R)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Hayk Davtyan (H)

Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
ORCID: 0000-0001-8554-6456

Howard L Weiner (HL)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Mathew Blurton-Jones (M)

Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
ORCID: 0000-0002-7770-7157

Hyun-Sik Yang (HS)

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-8318-0443

Bart J L Eggen (BJL)

Department of Biomedical Sciences, Section Molecular Neurobiology, University Medical Center Groningen, Groningen, The Netherlands.
ORCID: 0000-0001-8941-0353

Reisa A Sperling (RA)

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-1535-6133

Oleg Butovsky (O)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. obutovsky@bwh.harvard.edu.
Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA. obutovsky@bwh.harvard.edu.
ORCID: 0000-0003-0186-8867

Classifications MeSH