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

Abstract

Impaired clearance of amyloid beta (Abeta) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Abeta clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Abeta-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 Abeta-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Abeta 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 Abeta-binding monocytes may play a role in CNS Abeta clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.

Authors: Huang X, Fowler C, Li Y, Li QX, Sun J, Pan Y, Jin L, Perez KA, Dubois C, Lim YY, Drysdale C, Rumble RL, Chinnery HR, Rowe CC, Martins RN, Maruff P, Doecke JD, Lin Y, Belaidi AA, Barnham KJ, Masters CL, Gu BJ,
Journal: Nat Commun;2024Sep12; 15 (1) 7998. doi:10.1038/s41467-024-52396-1
Year: 2024
PubMed: PMID: 39266542 (Go to PubMed)