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

Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer’s disease
Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer’s disease
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-? (A?) 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 A? 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 A?. 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 A? and increase severity of CAA.
alzheimer’s disease, cerebral vasculature, perivascular drainage, basement membranes, immunotherapy
0001-6322
48-[11pp]
Carare, Roxana
0478c197-b0c1-4206-acae-54e88c8f21fa
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Hawkes, Cheryl A
5c3020ba-dd24-4316-b1b6-d6d43609d9e0
Püntener, Ursula
b645b3c6-e581-49b4-8ffb-7837f064b3ef
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Nicoll, James AR
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Perry, Victor
8f29d36a-8e1f-4082-8700-09483bbaeae4
Carare, Roxana
0478c197-b0c1-4206-acae-54e88c8f21fa
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Hawkes, Cheryl A
5c3020ba-dd24-4316-b1b6-d6d43609d9e0
Püntener, Ursula
b645b3c6-e581-49b4-8ffb-7837f064b3ef
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Nicoll, James AR
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Perry, Victor
8f29d36a-8e1f-4082-8700-09483bbaeae4

Carare, Roxana, Teeling, Jessica, Hawkes, Cheryl A, Püntener, Ursula, Weller, Roy O, Nicoll, James AR and Perry, Victor (2013) Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer’s disease. Acta Neuropathologica, 1 (1), 48-[11pp]. (doi:10.1186/2051-5960-1-48). (PMID:24252464)

Record type: Article

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-? (A?) 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 A? 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 A?. 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 A? and increase severity of CAA.

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More information

Published date: 9 August 2013
Keywords: alzheimer’s disease, cerebral vasculature, perivascular drainage, basement membranes, immunotherapy
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 359141
URI: https://eprints.soton.ac.uk/id/eprint/359141
ISSN: 0001-6322
PURE UUID: 29004bfe-f62b-4037-8c5c-d5481fdfaf63
ORCID for Jessica Teeling: ORCID iD orcid.org/0000-0003-4004-7391
ORCID for James AR Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 22 Oct 2013 13:53
Last modified: 19 Jul 2019 21:24

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Contributors

Author: Roxana Carare
Author: Jessica Teeling ORCID iD
Author: Cheryl A Hawkes
Author: Ursula Püntener
Author: Roy O Weller
Author: James AR Nicoll ORCID iD
Author: Victor Perry

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