This is a new paper from the Florey Institute by Prof. Masters et al. It is a free paper.

They demonstrate that blood monocytes of healthy people can clear brain amyloid much more than the monocytes of MCI and AD patients. This is a new way of explaining how amyloid is eliminated from brain.

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 ^{1 2}, Chris Fowler ¹, Yihan Li ¹, Qiao-Xin Li ^{1 3}, Jiaqi Sun ¹, Yijun Pan ¹, Liang Jin ¹, Keyla A Perez ¹, Céline Dubois ¹, Yen Y Lim ⁴, Candace Drysdale ¹, Rebecca L Rumble ¹, Holly R Chinnery ^{5 6 7}, Christopher C Rowe ⁸, Ralph N Martins ⁹, Paul Maruff ^{1 10}, James D Doecke ¹¹, Yong Lin ¹², Abdel A Belaidi ¹, Kevin J Barnham ¹, Colin L Masters ¹³, Ben J Gu ^{14 15 16}

Affiliations Expand

• PMID: 39266542

DOI: 10.1038/s41467-024-52396-1

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.