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A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration

Author

Listed:
  • Friederike Grandke

    (Saarland University)

  • Tobias Fehlmann

    (Saarland University)

  • Fabian Kern

    (Saarland University
    Saarland University Campus)

  • David M. Gate

    (Stanford University
    Veterans Administration Palo Alto Healthcare System
    Stanford University
    Stanford University)

  • Tobias William Wolff

    (Saarland University)

  • Olivia Leventhal

    (Stanford University)

  • Divya Channappa

    (Stanford University)

  • Pascal Hirsch

    (Saarland University)

  • Edward N. Wilson

    (Stanford University)

  • Eckart Meese

    (Saarland University)

  • Chuanyu Liu

    (MGI Group)

  • Quan Shi

    (MGI Group)

  • Matthias Flotho

    (Saarland University)

  • Yongping Li

    (Saarland University
    MGI Group)

  • Cynthia Chen

    (MGI Group)

  • Yeya Yu

    (MGI Group)

  • Jiangshan Xu

    (MGI Group)

  • Michael Junkin

    (MGI Group)

  • Zhifeng Wang

    (MGI Group)

  • Tao Wu

    (MGI Group)

  • Longqi Liu

    (MGI Group)

  • Yong Hou

    (MGI Group)

  • Katrin I. Andreasson

    (Stanford University
    Stanford University
    Stanford University)

  • Jenny S. Gansen

    (Saarland University)

  • Elvira Mass

    (University of Bonn)

  • Kathleen Poston

    (Stanford University)

  • Tony Wyss-Coray

    (Stanford University
    Veterans Administration Palo Alto Healthcare System
    Stanford University
    Stanford University)

  • Andreas Keller

    (Saarland University
    Saarland University Campus
    Stanford University
    Saarland University Campus)

Abstract

The clinical course and treatment of neurodegenerative disease are complicated by immune-system interference and chronic inflammatory processes, which remain incompletely understood. Mapping immune signatures in larger human cohorts through single-cell gene expression profiling supports our understanding of observed peripheral changes in neurodegeneration. Here, we employ single-cell gene expression profiling of over 909k peripheral blood mononuclear cells (PBMCs) from 121 healthy individuals, 48 patients with mild cognitive impairment (MCI), 46 with Parkinson’s disease (PD), 27 with Alzheimer’s disease (AD), and 15 with both PD and MCI. The dataset is interactively accessible through a freely available website ( https://www.ccb.uni-saarland.de/adrcsc ). In this work, we identify disease-associated changes in blood cell type composition and the gene expression in a sex-specific manner, offering insights into peripheral and solid tissue signatures in AD and PD.

Suggested Citation

  • Friederike Grandke & Tobias Fehlmann & Fabian Kern & David M. Gate & Tobias William Wolff & Olivia Leventhal & Divya Channappa & Pascal Hirsch & Edward N. Wilson & Eckart Meese & Chuanyu Liu & Quan Sh, 2025. "A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56833-7
    DOI: 10.1038/s41467-025-56833-7
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    1. Francisco J. Garcia & Na Sun & Hyeseung Lee & Brianna Godlewski & Hansruedi Mathys & Kyriaki Galani & Blake Zhou & Xueqiao Jiang & Ayesha P. Ng & Julio Mantero & Li-Huei Tsai & David A. Bennett & Must, 2022. "Single-cell dissection of the human brain vasculature," Nature, Nature, vol. 603(7903), pages 893-899, March.
    2. Andrew C. Yang & Ryan T. Vest & Fabian Kern & Davis P. Lee & Maayan Agam & Christina A. Maat & Patricia M. Losada & Michelle B. Chen & Nicholas Schaum & Nathalie Khoury & Angus Toland & Kruti Calcutta, 2022. "A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk," Nature, Nature, vol. 603(7903), pages 885-892, March.
    3. 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.
    4. Hansruedi Mathys & Jose Davila-Velderrain & Zhuyu Peng & Fan Gao & Shahin Mohammadi & Jennie Z. Young & Madhvi Menon & Liang He & Fatema Abdurrob & Xueqiao Jiang & Anthony J. Martorell & Richard M. Ra, 2019. "Single-cell transcriptomic analysis of Alzheimer’s disease," Nature, Nature, vol. 570(7761), pages 332-337, June.
    5. Andrew C. Yang & Marc Y. Stevens & Michelle B. Chen & Davis P. Lee & Daniel Stähli & David Gate & Kévin Contrepois & Winnie Chen & Tal Iram & Lichao Zhang & Ryan T. Vest & Aisling Chaney & Benoit Leha, 2020. "Physiological blood–brain transport is impaired with age by a shift in transcytosis," Nature, Nature, vol. 583(7816), pages 425-430, July.
    6. Hansruedi Mathys & Jose Davila-Velderrain & Zhuyu Peng & Fan Gao & Shahin Mohammadi & Jennie Z. Young & Madhvi Menon & Liang He & Fatema Abdurrob & Xueqiao Jiang & Anthony J. Martorell & Richard M. Ra, 2019. "Author Correction: Single-cell transcriptomic analysis of Alzheimer’s disease," Nature, Nature, vol. 571(7763), pages 1-1, July.
    7. Joel W. Blanchard & Leyla Anne Akay & Jose Davila-Velderrain & Djuna Maydell & Hansruedi Mathys & Shawn M. Davidson & Audrey Effenberger & Chih-Yu Chen & Kristal Maner-Smith & Ihab Hajjar & Eric A. Or, 2022. "APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes," Nature, Nature, vol. 611(7937), pages 769-779, November.
    8. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    9. Andrew C. Yang & Fabian Kern & Patricia M. Losada & Maayan R. Agam & Christina A. Maat & Georges P. Schmartz & Tobias Fehlmann & Julian A. Stein & Nicholas Schaum & Davis P. Lee & Kruti Calcuttawala &, 2021. "Dysregulation of brain and choroid plexus cell types in severe COVID-19," Nature, Nature, vol. 595(7868), pages 565-571, July.
    10. Andrew C. Yang & Fabian Kern & Patricia M. Losada & Maayan R. Agam & Christina A. Maat & Georges P. Schmartz & Tobias Fehlmann & Julian A. Stein & Nicholas Schaum & Davis P. Lee & Kruti Calcuttawala &, 2021. "Publisher Correction: Dysregulation of brain and choroid plexus cell types in severe COVID-19," Nature, Nature, vol. 598(7882), pages 4-4, October.
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