Real-Time In Vivo Imaging Reveals the Ability of Monocytes to Clear Vascular Amyloid Beta

• Ly6Clo monocytes are attracted to and crawl selectively onto Aβ-positive veins
• Monocytes take up Aβ and circulate back to the bloodstream
• Aβ deposition and elimination by monocytes is dynamic in veins of young APP/PS1 mice
• Ablation of Ly6Clo monocytes in APP/PS1 mice increases Aβ load

SummaryAlzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Aβ deposition within the cerebral vasculature. The contribution of monocytes in AD has so far been limited to macrophage precursors. In this study, we aimed to investigate whether circulating monocytes could play a role in the elimination of Aβ. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of Aβ-positive veins, but not on Aβ-positive arteries or Aβ-free blood vessels. Additionally, we report the presence of crawling monocytes carrying Aβ in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6Clo monocytes in APP/PS1 mice induced a significant increase of Aβ load in the cortex and hippocampus. These data uncover the ability of Ly6Clo monocytes to naturally target and eliminate Aβ within the lumen of veins and constitute a potential therapeutic target in AD.

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