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

Autor: Huang X; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.; The Innate Phagocytosis Laboratory, Level 11, Melbourne, Victoria, Australia., Fowler C; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Li Y; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Li QX; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.; National Dementia Diagnostics Laboratory, The University of Melbourne, Parkville, VIC, Australia., Sun J; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Pan Y; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Jin L; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Perez KA; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Dubois C; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Lim YY; Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia., Drysdale C; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Rumble RL; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Chinnery HR; 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., Rowe CC; Department of Nuclear Medicine and Center for PET, Austin Health, Heidelberg, VIC, Australia., Martins RN; Center of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia., Maruff P; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.; Cogstate Ltd., Melbourne, VIC, Australia., Doecke JD; Health and Biosecurity, Australian E-Health Research Center, CSIRO, Brisbane, QLD, Australia., Lin Y; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Belaidi AA; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Barnham KJ; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia., Masters CL; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia. c.masters@unimelb.edu.au., Gu BJ; The Florey Institute, The University of Melbourne, Parkville, VIC, Australia. ben.gu@innatephagolab.com.au.; The Innate Phagocytosis Laboratory, Level 11, Melbourne, Victoria, Australia. ben.gu@innatephagolab.com.au.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. ben.gu@innatephagolab.com.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 12; Vol. 15 (1), pp. 7998. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1038/s41467-024-52396-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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