NDLI: IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor.

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IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor.

Content Provider	Semantic Scholar
Author	Deane, R. Travis Sagare, Abhay P. Hamm, Katie Parisi, Margaret LaRue, Barbra Guo, Huang Wu, Zhenhua Holtzman, David M. Zlokovic, Berislav V.
Copyright Year	2005
Abstract	The role of blood-brain barrier (BBB) transport in clearance of amyloid beta-peptide (Abeta) by Abeta immunotherapy is not fully understood. To address this issue, we studied the effects of peripherally and centrally administered Abeta-specific IgG on BBB influx of circulating Abeta and efflux of brain-derived Abeta in APPsw(+/-) mice, a model that develops Alzheimer's disease-like amyloid pathology, and wild-type mice. Our data show that anti-Abeta IgG blocks the BBB influx of circulating Abeta in APPsw(+/-) mice and penetrates into the brain to sequester brain Abeta. In young mice, Abeta-anti-Abeta complexes were cleared from brain to blood by transcytosis across the BBB via the neonatal Fc receptor (FcRn) and the low-density lipoprotein receptor-related protein (LRP), whereas in older mice, there was an age-dependent increase in FcRn-mediated IgG-assisted Abeta BBB efflux and a decrease in LRP-mediated clearance of Abeta-anti-Abeta complexes. Inhibition of the FcRn pathway in older APPsw(+/-) mice blocked clearance of endogenous Abeta40/42 by centrally administered Abeta immunotherapy. Moreover, deletion of the FcRn gene in wild-type mice inhibited clearance of endogenous mouse Abeta40/42 by systemically administered anti-Abeta. Our data suggest that the FcRn pathway at the BBB plays a crucial role in IgG-assisted Abeta removal from the aging brain.
File Format	PDF HTM / HTML
DOI	10.1523/JNEUROSCI.3697-05.2005
Alternate Webpage(s)	http://www.jneurosci.org/content/jneuro/25/50/11495.full.pdf
PubMed reference number	16354907
Alternate Webpage(s)	https://doi.org/10.1523/JNEUROSCI.3697-05.2005
Journal	Medline
Volume Number	25
Issue Number	50
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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