Abeta species removal after abeta42 immunization

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 abundan...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2006-11, Vol.65 (11), p.1040-1048
Main Authors: Nicoll, James A R, Barton, Edward, Boche, Delphine, Neal, Jim W, Ferrer, Isidro, Thompson, Petrina, Vlachouli, Christina, Wilkinson, David, Bayer, Antony, Games, Dora, Seubert, Peter, Schenk, Dale, Holmes, Clive
Format: Article
Language:English
Subjects:
Alzheimer Disease - immunology
Alzheimer Disease - pathology
Alzheimer Disease - therapy
Alzheimer Vaccines - immunology
Alzheimer Vaccines - therapeutic use
Amino Acid Sequence
Amyloid beta-Peptides - genetics
Amyloid beta-Peptides - immunology
Amyloid beta-Peptides - therapeutic use
Brain - pathology
Cerebral Amyloid Angiopathy - pathology
Humans
Image Processing, Computer-Assisted
Immunohistochemistry
Microglia - pathology
Microscopy, Confocal
Molecular Sequence Data
Neurofibrillary Tangles - pathology
Neuropil Threads - pathology
Peptide Fragments - immunology
Peptide Fragments - therapeutic use
Phagocytosis
Randomized Controlled Trials as Topic
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Summary: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.
ISSN:0022-3069