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

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (A beta) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of A beta 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 A beta. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of A beta-positive veins, but not on A beta-positive arteries or A beta-free blood vessels. Additionally, we report the presence of crawling monocytes carrying A beta in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6C(lo) monocytes in APP/PS1 mice induced a significant increase of A beta load in the cortex and hippocampus. These data uncover the ability of Ly6C(lo) monocytes to naturally target and eliminate A beta within the lumen of veins and constitute a potential therapeutic target in AD.