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Clearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer’s disease progression

Author

Listed:
  • Xin Huang

    (The University of Melbourne
    Level 11)

  • Chris Fowler

    (The University of Melbourne)

  • Yihan Li

    (The University of Melbourne)

  • Qiao-Xin Li

    (The University of Melbourne
    The University of Melbourne)

  • Jiaqi Sun

    (The University of Melbourne)

  • Yijun Pan

    (The University of Melbourne)

  • Liang Jin

    (The University of Melbourne)

  • Keyla A. Perez

    (The University of Melbourne)

  • Céline Dubois

    (The University of Melbourne)

  • Yen Y. Lim

    (Monash University)

  • Candace Drysdale

    (The University of Melbourne)

  • Rebecca L. Rumble

    (The University of Melbourne)

  • Holly R. Chinnery

    (The University of Melbourne
    Lions Eye Institute
    The University of Western Australia)

  • Christopher C. Rowe

    (Austin Health)

  • Ralph N. Martins

    (Edith Cowan University)

  • Paul Maruff

    (The University of Melbourne
    Cogstate Ltd.)

  • James D. Doecke

    (Australian E-Health Research Center, CSIRO)

  • Yong Lin

    (Fudan University)

  • Abdel A. Belaidi

    (The University of Melbourne)

  • Kevin J. Barnham

    (The University of Melbourne)

  • Colin L. Masters

    (The University of Melbourne)

  • Ben J. Gu

    (The University of Melbourne
    Level 11
    Fudan University)

Abstract

Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer’s disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aβ-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Aβ levels in mild cognitive impairment (MCI) and AD-dementia patients compared to cognitively unimpaired individuals. Monocyte infiltration from blood to CSF and migration from CNS to peripheral lymph nodes and blood are observed. Here we show that Aβ-binding monocytes may play a role in CNS Aβ clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.

Suggested Citation

  • Xin Huang & Chris Fowler & Yihan Li & Qiao-Xin Li & Jiaqi Sun & Yijun Pan & Liang Jin & Keyla A. Perez & Céline Dubois & Yen Y. Lim & Candace Drysdale & Rebecca L. Rumble & Holly R. Chinnery & Christo, 2024. "Clearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer’s disease progression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52396-1
    DOI: 10.1038/s41467-024-52396-1
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    References listed on IDEAS

    as
    1. Mitchell H. Murdock & Cheng-Yi Yang & Na Sun & Ping-Chieh Pao & Cristina Blanco-Duque & Martin C. Kahn & TaeHyun Kim & Nicolas S. Lavoie & Matheus B. Victor & Md Rezaul Islam & Fabiola Galiana & Noell, 2024. "Multisensory gamma stimulation promotes glymphatic clearance of amyloid," Nature, Nature, vol. 627(8002), pages 149-156, March.
    2. Akinori Nakamura & Naoki Kaneko & Victor L. Villemagne & Takashi Kato & James Doecke & Vincent Doré & Chris Fowler & Qiao-Xin Li & Ralph Martins & Christopher Rowe & Taisuke Tomita & Katsumi Matsuzaki, 2018. "High performance plasma amyloid-β biomarkers for Alzheimer’s disease," Nature, Nature, vol. 554(7691), pages 249-254, February.
    Full references (including those not matched with items on IDEAS)

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