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Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer's disease

Carare, Roxana Octavia; Teeling, Jessica Liesbeth; Hawkes, Cheryl A.; Püntener, Ursula; Weller, Roy O.; Nicoll, James A. R. and Perry, Victor Hugh (2013). Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer's disease. Acta neuropathologica communications, 1(1), article no. 48.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1186/2051-5960-1-48
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Abstract

Background: Basement membranes in the walls of cerebral capillaries and arteries form a major lymphatic drainage pathway for fluid and solutes from the brain. Amyloid-β (Aβ) draining from the brain is deposited in such perivascular pathways as cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). CAA increases in severity when Aβ is removed from the brain parenchyma by immunotherapy for AD. In this study we investigated the consequences of immune complexes in artery walls upon drainage of solutes similar to soluble Aβ. We tested the hypothesis that, following active immunization with ovalbumin, immune complexes form within the walls of cerebral arteries and impair the perivascular drainage of solutes from the brain. Mice were immunized against ovalbumin and then challenged by intracerebral microinjection of ovalbumin. Perivascular drainage of solutes was quantified following intracerebral microinjection of soluble fluorescent 3kDa dextran into the brain at different time intervals after intracerebral challenge with ovalbumin.

Results: Ovalbumin, IgG and complement C3 co-localized in basement membranes of artery walls 24 hrs after challenge with antigen; this was associated with significantly reduced drainage of dextran in immunized mice.

Conclusions: Perivascular drainage along artery walls returned to normal by 7 days. These results indicate that immune complexes form in association with basement membranes of cerebral arteries and interfere transiently with perivascular drainage of solutes from the brain. Immune complexes formed during immunotherapy for AD may similarly impair perivascular drainage of soluble Aβ and increase severity of CAA.

Item Type: Journal Item
Copyright Holders: 2013 Carare et al.
ISSN: 2051-5960
Keywords: Alzheimer’s disease; cerebral vasculature; perivascular drainage; basement membranes; immunotherapy
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 44087
Depositing User: Cheryl Hawkes
Date Deposited: 10 Sep 2015 09:34
Last Modified: 07 Dec 2018 20:43
URI: http://oro.open.ac.uk/id/eprint/44087
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