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

Impaired clearance of amyloid beta (A beta) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in A beta clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify A beta-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 A beta-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface A beta 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 A beta-binding monocytes may play a role in CNS A beta clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring. Impaired A beta clearance in late-onset Alzheimer's disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry A beta in peripheral circulation and CSF in AD, suggesting a role in A beta clearance.