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

X Huang; C Fowler; Y Li; QX Li; J Sun; Y Pan; L Jin; KA Perez; C Dubois; YY Lim; C Drysdale; RL Rumble; HR Chinnery; CC Rowe; RN Martins; P Maruff; JD Doecke; Y Lin; AA Belaidi; KJ Barnham; CL Masters; BJ Gu

Journal article

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

X Huang, C Fowler, Y Li, QX Li, J Sun, Y Pan, L Jin, KA Perez, C Dubois, YY Lim, C Drysdale, RL Rumble, HR Chinnery, CC Rowe, RN Martins, P Maruff, JD Doecke, Y Lin, AA Belaidi, KJ Barnham Show all

Nature Communications | NATURE PORTFOLIO | Published : 2024

DOI: 10.1038/s41467-024-52396-1

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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..

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University of Melbourne Researchers

Qiao-Xin Li Author

Holly Chinnery Author

Christopher Rowe Author

Paul Maruff Author

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Awarded by State Government of Victoria

Funding Acknowledgements

We thank Dr. Verena Wimmer and Dr. Carolina Chavez for their help with confocal microscopy. This work was supported by National Health and Medical Research Council (NHMRC) Project Grants - 2016803 to (Masters); ARC Future Fellowship FT120100581 (to Gu), NHMRC Project Grants - 1048082, 1061419, 1120095, and 110178 (to Gu), and State Government of Victoria (Victorian Government) - Operational Infrastructure Support Grant to the Florey Institute.