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Effects of Abeta immunotherapy on cerebral amyloid angiopathy in Alzheimer’s disease

Effects of Abeta immunotherapy on cerebral amyloid angiopathy in Alzheimer’s disease
Effects of Abeta immunotherapy on cerebral amyloid angiopathy in Alzheimer’s disease
Introduction: In Alzheimer’s disease (AD) A? accumulates as plaques in the cerebral cortex and in blood vessel walls (cerebral amyloid angiopathy, CAA). Animal and human studies show that accumulation of A? plaques can be reversed by immunotherapy. We hypothesized that A? in plaques is solubilized following immunization and drains via the perivascular pathway therefore increasing CAA severity.

Materials and methods: Immunostaining for A?40 and 42 was quantified on four patients who had been immunized with A? as participants in the Elan Pharmaceuticals trial and compared with 6 un-immunized AD patients.

Results: The CAA was substantially more severe in three immunized patients who had evidence of plaque removal than in the un-immunized AD cases. One immunized patient without evidence of plaque removal had a CAA severity similar to un-immunized AD. Consistent with our hypothesis, there was an increase in the density of cortical vessels containing A?42, a major component of plaques. However, there was also a corresponding increase in the density of vessels containing A?40. In addition, the immunized AD patients showed a higher density of cortical microhaemorrhages than the un-immunized AD controls.

Conclusion: Plaque removal following A? immunization in AD is associated with an increased severity of CAA.
alzheimer's disease, immunotherapy, disease, cerebral amyloid angiopathy
223-224
Boche, D.
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Barton, E.
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Neal, J.
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Ferrer, I.
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Wilkinson, D.
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Bayer, A.
591af99a-3842-4382-ad46-d3ed798fca41
Holmes, C.
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Weller, R.O.
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Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Barton, E.
827291d4-3de9-4770-9f7a-5aba44a9c34a
Neal, J.
c51b1599-d133-4c5c-bc30-75811235e314
Ferrer, I.
410a941d-a6dd-46d6-a8c9-8ae74c8778d0
Wilkinson, D.
917ddca3-1dba-4e3c-8618-4db1f8b11800
Bayer, A.
591af99a-3842-4382-ad46-d3ed798fca41
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed

Boche, D., Barton, E., Neal, J., Ferrer, I., Wilkinson, D., Bayer, A., Holmes, C., Weller, R.O. and Nicoll, J.A.R. (2006) Effects of Abeta immunotherapy on cerebral amyloid angiopathy in Alzheimer’s disease. Proceedings of the 107th Meeting of the British Neuropathological Society, United Kingdom. 11 - 13 Jan 2006. pp. 223-224 . (doi:10.1111/j.1365-2990.2006.00749.x).

Record type: Conference or Workshop Item (Paper)

Abstract

Introduction: In Alzheimer’s disease (AD) A? accumulates as plaques in the cerebral cortex and in blood vessel walls (cerebral amyloid angiopathy, CAA). Animal and human studies show that accumulation of A? plaques can be reversed by immunotherapy. We hypothesized that A? in plaques is solubilized following immunization and drains via the perivascular pathway therefore increasing CAA severity.

Materials and methods: Immunostaining for A?40 and 42 was quantified on four patients who had been immunized with A? as participants in the Elan Pharmaceuticals trial and compared with 6 un-immunized AD patients.

Results: The CAA was substantially more severe in three immunized patients who had evidence of plaque removal than in the un-immunized AD cases. One immunized patient without evidence of plaque removal had a CAA severity similar to un-immunized AD. Consistent with our hypothesis, there was an increase in the density of cortical vessels containing A?42, a major component of plaques. However, there was also a corresponding increase in the density of vessels containing A?40. In addition, the immunized AD patients showed a higher density of cortical microhaemorrhages than the un-immunized AD controls.

Conclusion: Plaque removal following A? immunization in AD is associated with an increased severity of CAA.

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More information

e-pub ahead of print date: 13 March 2006
Published date: April 2006
Venue - Dates: Proceedings of the 107th Meeting of the British Neuropathological Society, United Kingdom, 2006-01-11 - 2006-01-13
Keywords: alzheimer's disease, immunotherapy, disease, cerebral amyloid angiopathy

Identifiers

Local EPrints ID: 62328
URI: https://eprints.soton.ac.uk/id/eprint/62328
PURE UUID: d0a289a9-58f7-4cbe-a033-5b1b4d1340a6
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for C. Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for J.A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 21 Apr 2009
Last modified: 14 Mar 2019 01:48

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Contributors

Author: D. Boche ORCID iD
Author: E. Barton
Author: J. Neal
Author: I. Ferrer
Author: D. Wilkinson
Author: A. Bayer
Author: C. Holmes ORCID iD
Author: R.O. Weller
Author: J.A.R. Nicoll ORCID iD

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