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2024

Nat Commun. 2024 Sep 12;15(1):7998. doi: 10.1038/s41467-024-52396-1.

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

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, Christopher C Rowe, Ralph N Martins, Paul Maruff, James D Doecke, Yong Lin, Abdel A Belaidi, Kevin J Barnham, Colin L Masters, Ben J Gu

The Florey Institute, The University of Melbourne, Parkville, VIC, Australia. The Innate Phagocytosis Laboratory, Level 11, Melbourne, Victoria, Australia. National Dementia Diagnostics Laboratory, The University of Melbourne, Parkville, VIC, Australia. Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia. Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia. Lions Eye Institute, Perth, Western Australia, Australia. Optometry, School of Allied Health, The University of Western Australia, Perth, Australia. Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, VIC, Australia. Center of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia. Cogstate Ltd., Melbourne, VIC, Australia. Health and Biosecurity, Australian E-Health Research Center, CSIRO, Brisbane, QLD, Australia. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Service type: Stock strains

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.

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