Abeta species removal after abeta42 immunization

Nicoll, James A. R., Barton, Edward, Boche, Delphine, Neal, James William, Ferrer, Isidro, Thompson, Petrina, Vlachouli, Christina, Wilkinson, David, Bayer, Antony James ORCID: https://orcid.org/0000-0002-7514-248X, Games, Dora, Seubert, Peter, Schenk, Dale and Holmes, Clive 2006. Abeta species removal after abeta42 immunization. Journal of Neuropathology and Experimental Neurology 65 (11) , pp. 1040-1048. 10.1097/01.jnen.0000240466.10758.ce

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Abstract

Neuropathologic examination of 3 patients with Alzheimer disease in the Elan Pharmaceuticals trial using antibodies specific for different Abeta species showed in one case, 4 months after the immunization, evidence of a stage of active plaque clearance with "moth-eaten" plaques and abundant Abeta phagocytosis by microglia. At 1 to 2 years after immunization, 2 cases showed extensive areas cleared of plaques (69% and 86% of the temporal cortex was plaque-free). Cortex cleared of plaques in all 3 cases had a characteristic constellation of features, including a very low plaque burden, sparse residual dense plaque cores, and phagocytosed Abeta within microglia. There was resolution of tau-containing dystrophic neurites, although other features of tau pathology (tangles and neuropil threads) remained and cerebral amyloid angiopathy persisted. Although most antibodies generated by Abeta42 immunization in humans bind the intact N-terminus, immunohistochemistry with specific antibodies showed clearance of all major species of Abeta (Abeta40, Abeta42, and N-terminus truncated Abeta). Abeta immunotherapy can clear all Abeta species from the cortex. However, if it is to be used for treatment of established Alzheimer disease, then the residual tau pathology and cerebral amyloid angiopathy require further study.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Lippincott Williams & Wilkins
ISSN:	0022-3069
Last Modified:	24 Oct 2022 10:36
URI:	https://orca.cardiff.ac.uk/id/eprint/45068

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