Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta
- PMID: 24210819
- DOI: 10.1016/j.celrep.2013.10.010
Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta
Abstract
Alzheimer'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 Ly6C(lo) monocytes in APP/PS1 mice induced a significant increase of Aβ load in the cortex and hippocampus. These data uncover the ability of Ly6C(lo) monocytes to naturally target and eliminate Aβ within the lumen of veins and constitute a potential therapeutic target in AD.
Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Similar articles
-
Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities.Alzheimers Dement. 2013 Oct;9(5 Suppl):S105-15. doi: 10.1016/j.jalz.2012.11.010. Epub 2013 Apr 11. Alzheimers Dement. 2013. PMID: 23583235
-
Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice.Neurobiol Dis. 2006 Sep;23(3):653-62. doi: 10.1016/j.nbd.2006.05.010. Epub 2006 Jul 10. Neurobiol Dis. 2006. PMID: 16829076
-
Alpha7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of Abeta peptides and promotes cerebrovascular amyloid angiopathy.Brain Res. 2008 Oct 9;1234:158-71. doi: 10.1016/j.brainres.2008.07.092. Epub 2008 Aug 3. Brain Res. 2008. PMID: 18708033
-
Alzheimer's disease.Subcell Biochem. 2012;65:329-52. doi: 10.1007/978-94-007-5416-4_14. Subcell Biochem. 2012. PMID: 23225010 Review.
-
Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer's disease. Pro-CAA position statement.Neurobiol Aging. 2004 May-Jun;25(5):589-97; discussion 603-4. doi: 10.1016/j.neurobiolaging.2004.02.003. Neurobiol Aging. 2004. PMID: 15172734 Review.
Cited by
-
Nonclassical patrolling monocyte function in the vasculature.Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1306-16. doi: 10.1161/ATVBAHA.114.304650. Epub 2015 Apr 2. Arterioscler Thromb Vasc Biol. 2015. PMID: 25838429 Free PMC article. Review.
-
Blood Leukocyte Counts in Alzheimer Disease.JAMA Netw Open. 2022 Oct 3;5(10):e2235648. doi: 10.1001/jamanetworkopen.2022.35648. JAMA Netw Open. 2022. PMID: 36215071 Free PMC article.
-
Role of P2X7 Receptors in Immune Responses During Neurodegeneration.Front Cell Neurosci. 2021 May 26;15:662935. doi: 10.3389/fncel.2021.662935. eCollection 2021. Front Cell Neurosci. 2021. PMID: 34122013 Free PMC article. Review.
-
Comparative Review of Microglia and Monocytes in CNS Phagocytosis.Cells. 2021 Sep 27;10(10):2555. doi: 10.3390/cells10102555. Cells. 2021. PMID: 34685535 Free PMC article. Review.
-
Acute Effects of Focused Ultrasound-Induced Blood-Brain Barrier Opening on Anti-Pyroglu3 Abeta Antibody Delivery and Immune Responses.Biomolecules. 2022 Jul 6;12(7):951. doi: 10.3390/biom12070951. Biomolecules. 2022. PMID: 35883506 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
